Bio


Born in Philadelphia, Pennsylvania, Barry Trost began his university training at the University of Pennsylvania (BA, 1962) and completed his Ph.D. in Chemistry at the Massachusetts Institute of Technology (1965). He moved directly to the University of Wisconsin, where he was promoted to Professor of Chemistry and subsequently Vilas Research Professor. He joined the faculty at Stanford as Professor of Chemistry in 1987 and became Tamaki Professor of Humanities and Sciences in 1990. In addition to serving multiple visiting professorships, Professor Trost was presented with a Docteur honoris causa of the Université Claude-Bernard (Lyon I), France, and in 1997 a Doctor Scientiarum Honoris Causa of the Technion, Haifa, Israel. In recognition of his innovations and scholarship in the field of organic synthesis, Professor Trost has received the ACS Award in Pure Chemistry, ACS Award for Creative Work in Synthetic Organic Chemistry, Arthur C. Cope Scholar Award, and the Presidential Green Chemistry Challenge Award, among many others. Professor Trost has been elected a Fellow of the American Academy of Arts and Sciences, American Chemical Society, and American Association for the Advancement of Science, and a member of the National Academy of Sciences, and served as Chairman of the NIH Medicinal Chemistry Study Section. He has held over 125 special university lectureships and presented over 270 Plenary Lectures at national and international meetings. He has published two books and over 950 scientific articles. He edited a major compendium entitled Comprehensive Organic Synthesis consisting of nine volumes and serves on the editorial board for Science of Synthesis and Reaxys.

The Trost Group’s research program revolves around the theme of synthesis, including target molecules with potential applications as novel catalysts, as well as antibiotic and antitumor therapies. The work comprises two major activities: 1) developing the tools, i.e., the reactions and reagents, and 2) creating the proper network of reactions to make complex targets readily available from simple starting materials.

Efforts to develop "chemists' enzymes" – non-peptidic transition metal based catalysts that can perform chemo-, regio-, diastereo-, and especially enantioselective reactions – focus close attention to the question of atom economy to minimize waste, energy, and consumption of raw materials.

Synthetic efficiency raises the question of metal catalyzed cycloadditions to rings other than six-membered. A general strategy is evolving for a "Diels-Alder" equivalent for formation of five, seven, nine, etc. membered carbo- and heterocyclic rings.

An exciting new direction derives from the molecular gymnastics acetylenes undergo in the presence of transition metals. Additional specific goals include cycloisomerization to virtually all types of ring sizes and systems with particularly versatile juxtaposition of functionality.

Palladium and ruthenium catalysts represent a major part of the lab's efforts, in order to invent new synthetic processes together with new opportunities for selectivity complementary to that obtained using other metal complexes. Main group chemistry, especially involving silicon, zinc, and sulfur, also offers many opportunities for new reaction design. Rational design of novel catalysts for asymmetric additions to carbonyl and imine groups are an exciting thrust.From these new synthetic tools evolve new synthetic strategies towards complex natural products. Targets include β-lactam antibiotics, ionophores, steroids and related compounds (e.g., Vitamin D metabolites), alkaloids, nucleosides, carbohydrates, and macrolide, terpenoid, and tetracyclic antitumor and antibiotic agents.

Academic Appointments


Honors & Awards


  • Linus Pauling Medal Award, Puget Sound, Oregon, and Portland Sections of the American Chemical Society (2015)
  • Tetrahedron Prize, Tetrahedron Publications, Elsevier (2014)
  • August-Wilhelm-von-Hofmann Denkmuenze, German Chemical Society (2014)
  • Ryoji Noyori Prize, Society of Synthetic Organic Chemistry, Japan (2013)
  • Arthur C. Cope Award, American Chemical Society (2004)
  • Herbert C. Brown Award for Creative Research in Synthetic Methods, American Chemical Society (1999)
  • Presidential Green Chemistry Challenge Award, US EPA Office of Chemical Safety and Pollution Prevention (1998)
  • Roger Adams Award, American Chemical Society (1995)
  • Award for Creative Work in Synthetic Organic Chemistry, American Chemical Society (1981)
  • Award in Pure Chemistry, American Chemical Society (1977)
  • Junichiro Tanaka Distinguished Achievement Award, International Precious Metal Institute (2014)
  • Distinguished Alumni Award, Penn Chemistry (2013)
  • Excellence in Medicinal Chemistry Award, Israel Chemistry Society (2013)
  • Fellow, American Chemical Society (2012)
  • Kitasato Microbial Chemistry Medal, Kitasato Institute (2008)
  • Kosolapoff Award, Auburn Section, American Chemical Society (2008)
  • Nagoya Medal, Banyu Life Sci. Foundation Int’l and Institute of Transformative Bio-Molecules, Nagoya U. (2008)
  • Thomson Scientific Laureate, Thomson Reuters (2007)
  • John C. Scott Award, City of Philadelphia (2004)
  • Nobel Laureate Signature Award for Graduate Education, American Chemical Society (2002)
  • Yamada Prize, Japan (2001)
  • Elsevier Award, Belgium Organic Synthesis Symposium (2000)
  • Nichols Medal, New York Section, American Chemical Society (2000)
  • Merck-Schuchardt Lecturer, French Chemical Society (1998)
  • SCI-ACS (Joint Italian-American Chemical Societies) Lecturer, Joint Italian-American Chemical Societies (1998)
  • Doctor Scientiarum Honoris Causa, Technion, Haifa, Israel (1997)
  • Docteur Honoris Causa, Université Claude Bernard (Lyon-I), France (1994)
  • Bing Teaching Award, Stanford University (1993)
  • Pfizer Senior Faculty Award, Pfizer Corporation (1992)
  • ASSU Graduate Teaching Award, Stanford University (1991)
  • Dr. Paul Janssen Prize for Creativity in Organic Synthesis, Belgian Organic Synthesis Symposium (1990)
  • Ernest Guenther Award in the Chemistry of Essential Oils and Related Products, American Chemical Society (1990)
  • Arthur C. Cope Scholar Award, American Chemical Society (1989)
  • Hamilton Award, University of Nebraska (1988)
  • MERIT Award of the National Institutes of General Medical Sciences, National Institutes of Health (1988)
  • Nebraska Admiral, State of Nebraska (1988)
  • Kentucky Colonel, State of Kentucky (1987)
  • Alexander von Humboldt Stiftung Award, Alexander von Humboldt-Stiftung/Foundation (1984)
  • Chemical Pioneer, American Institute of Chemists (1983)
  • First Allen R. Day Award, Philadelphia Organic Chemist's Club (1983)
  • Medal of the University of Helsinki, University of Helsinki (1983)
  • Fellow, American Academy of Arts & Sciences (1982)
  • Centenary Lecturer, Royal Society of Chemistry, UK (1981-82)
  • Baekeland Award, North Jersey Section, American Chemical Society (1981)
  • Julius Stieglitz Memorial Lecturer, Chicago Section, American Chemical Society (1980-81)
  • Member, National Academy of Sciences (1980)
  • Fellow, American Association for Advancement of Science (1977)
  • Fellow, American–Swiss Foundation (1975)
  • H.I. Romnes Faculty Fellowship, UW–Madison Wisconsin Alumni Research Foundation (1975)
  • Dreyfus Teacher–Scholar, Camille & Henry Dreyfus Foundation (1970-75)
  • Sloan Fellow, Alfred P. Sloan Foundation (1967-69)

Boards, Advisory Committees, Professional Organizations


  • Editorial Advisory Board Member, Reaxys (CrossFire Beilstein) Database (2007 - Present)
  • Member, CAL/EPA Green Chemistry Scientific Advisory Panel (2007 - 2007)
  • Member, NRC Committee on the Review of Basic Energy Sciences Catalysis Program (2007 - 2007)
  • Editorial Board Member, Chemistry - An Asian Journal (2006 - Present)
  • Editorial Advisory Board Member, Beilstein Journal of Organic Chemistry (2005 - Present)
  • Editorial oard Member, Central European Journal of Chemistry (2003 - Present)
  • Editorial Board Member, Proceedings of the National Academy of Sciences (2003 - 2006)
  • Editorial Advisory Board, Journal of Organic Chemistry (2002 - 2006)
  • Organizing Committee, Mesilla Conference (2002 - 2002)
  • Editorial Advisory Board Member, Accounts of Chemical Research (2001 - 2003)
  • Visiting Committee, Department of Chemistry, Vanderbilt University (2001 - 2001)
  • Editorial Advisory Board Member, Advanced Synthesis and Catalysis (2000 - Present)
  • Member, NRC Advisory Board for the Division on Engineering and Physical Sciences (2000 - 2002)
  • Member, NICHD Review Panel (2000 - 2000)
  • Visiting Committee Member, Department of Chemistry, U. of Pennsylvania (2000 - 2000)
  • Editorial Advisory Board Member, Organic Letters (1999 - Present)
  • Editorial Board Member, Green Chemistry (1999 - Present)
  • Editorial Board Member, Natural Products Letters (1998 - Present)
  • Member, Committee of Visitors, Division of Chemistry, National Science Foundation (1998 - 1998)
  • Program Review Committee Member, Weizmann Institute of Science, Israel (1998 - 1998)
  • International Advisory Board Member, Current Organic Chemistry (1997 - Present)
  • Jury Member, Springer Award for Organometallic Chemistry (1997 - 1997)
  • Advisory Board Member, Bulletin de la Société Chimique de France (1996 - 1997)
  • Editor, Foundations of Organic Chemistry series, Thieme Verlag (1995 - Present)
  • Editorial Board Member, Chemistry - A European Journal (1995 - Present)
  • Editorial Board Member, Science of Synthesis, Houben-Weyl Methods of Molecular Transformations (1995 - Present)
  • Member, National Research Council Commission on Engineering and Technical Systems (1994 - 2000)
  • Editor, Stereocontrolled Organic Synthesis. Chemistry of the 21st Century, IUPAC Blackwell Scientific Pubs (1994 - 1994)
  • Jury Member, Thieme-IUPAC Prize in Synthetic Organic Chemistry (1994 - 1994)
  • Organizer, US-Former Soviet Union Workshop on Organic Synthesis, Stanford (1994 - 1994)
  • Visiting Committee Member, Department of Chemistry, Texas A&M University (1994 - 1994)
  • Editor, CHEMTRACTS-Organic Chemistry (1993 - Present)
  • Visiting Committee Member, Department of Chemistry, University of Pittsburgh (1993 - 1993)
  • Editorial Board Member, Natural Products Letters (1992 - 2002)
  • Member, Tetrahedron Board of Consulting Editors (1992 - 2002)
  • International Editorial Board Member, Journal of the Chemical Society-Perkin I (1992 - 1997)
  • Canvassing Committee, ACS Cope Award (1992 - 1995)
  • Member, NRC Committee on Alternative Chemical Demilitarization Technologies (1992 - 1993)
  • Chairman, Visiting Committee for Department of Chemistry, Iowa State U. (1991 - 1991)
  • Editor-in-Chief, Comprehensive Organic Synthesis, Pergamon Press (1991 - 1991)
  • Member, Board of Editors, Heteroatom Chemistry (1989 - Present)
  • Member, Editorial Advisory Board, Chemical & Engineering News (1989 - 1992)
  • Member, Ciba Foundation Discussion on Molecular Recognition in Synthesis (1988 - 1988)
  • Member, NIH Institute of General Medical Sciences Council Ad-Hoc Member (1988 - 1988)
  • Member, NSF Presidential Young Investigator Panel (1988 - 1988)
  • Visiting Committee Member, Department of Chemistry, Ohio State University (1988 - 1988)
  • Member, International Advisory Committee, VI International Conference on Organic Synthesis, Moscow, USSR (1986 - 1986)
  • U.S. Organizer, U.S.-Swedish Joint Seminar on Synthetic Selectivity, Tynningo, Sweden (1986 - 1986)
  • Award Committee Member, American Institute of Chemists' Chemical Pioneers Award (1985 - Present)
  • Member, American Academy of Arts and Sciences-Midwest Center Council (1985 - Present)
  • Member, Editorial Advisory Board, Synthesis (1985 - 2008)
  • Participant Selection Committee Member, NSF Organometallic Chemistry Workshop (1985 - 1985)
  • Visiting Committee Member, Department of Chemistry, University of Michigan (1985 - 1985)
  • Chairman, Review Committee for Department of Chemistry, U. Michigan (1984 - 1984)
  • Editor, with W. Bartmann, Selectivity - A Goal for Synthetic Efficiency, Verlag Chemie (1984 - 1984)
  • One of Five Invited U.S. Participants, U.S.-Swedish Workshop on the Future of Chemistry (1984 - 1984)
  • Canvassing Committee Member, Roger Adams Award in Organic Chemistry (1983 - 1989)
  • Member, Research Briefing Panel on Chemistry, National Academy of Sciences (1983 - 1983)
  • Scientific Organizer, Hoechst Workshop, Reisensburg, West Germany (1983 - 1983)
  • Member and Chairman (1984-6), NIH Medicinal Chemistry A Study Section (1982 - 1986)
  • Member, Swedish Natural Science Research Council and Swedish Board for Technical Development Review Panel on Organic and Bioorganic Chemistry (1982 - 1982)
  • Science Advisory Council Member, ARCO (1981 - 1987)
  • Member, Editorial Advisory Board, Organometallics (1981 - 1985)
  • Technical Advisory Panel Member, Indicators of Scientific Research Instrumentation in Academic Institutions (1981 - 1983)
  • Editor, with C.R. Hutchinson, Synthesis Today and Tomorrow, Pergamon Press (1981 - 1981)
  • Member, Committee on Chemical Sciences, National Academy of Sciences (1980 - 1983)
  • Award Committee Member, ACS Award for Creative Work in Synthetic Organic Chemistry (1980 - 1982)
  • Organizing Committee Chairman, 3rd IUPAC Symposium on Organic Synthesis (1980 - 1980)
  • U.S. Delegation to People's Republic of China, Chemistry of Natural Products (1980 - 1980)
  • Jury Member, ACS Chicago Section Willard Gibbs Medal (1979 - 1985)
  • Evaluation Panel Member, NRC Postdoctoral Fellowships (1978 - 1978)
  • Executive Committee Member, ACS Division of Organic Chemistry (1977 - 1979)
  • Organizing Committee Member, Roussel "Table Ronde" on Selectivity in Organic Synthesis (1977 - 1978)
  • Associate Editor, Journal of the American Chemical Society (1974 - 1980)
  • Advisory Panel Member, NSF Chemistry Section (1973 - 1977)
  • Member, Advisory Board of Editors, Journal of Organic Chemistry (1973 - 1977)
  • Member, Active Editorial Board, Organic Reactions Series (books) (1972 - 1981)
  • Canvassing Committee Member and Chairman, ACS Award for Creative Work in Synthetic Organic Chemistry (1972 - 1976)

Professional Education


  • PhD, Massachusetts Institute of Technology, Chemistry (1965)
  • BA with honors, University of Pennsylvania, Chemistry (1962)

2018-19 Courses


Stanford Advisees


All Publications


  • Desymmetrization of Phosphinic Acids via Pd-Catalyzed Asymmetric Allylic Alkylation: Rapid Access to P-Chiral Phosphinates. Journal of the American Chemical Society Trost, B. M., Spohr, S. M., Rolka, A. B., Kalnmals, C. A. 2019

    Abstract

    The synthesis of P-chiral compounds is challenging, especially since useful catalytic methods for preparing such molecules are scarce. Herein we disclose a desymmetrization that employs phosphinic acids as prochiral nucleophiles in a Pd-catalyzed asymmetric allylic alkylation reaction, furnishing phosphinates with high enantio- and diastereoselectivity. This new method has broad scope and is applied to the synthesis of an enantioenriched tertiary phosphine oxide.

    View details for DOI 10.1021/jacs.9b07340

    View details for PubMedID 31442377

  • Dinuclear Metal-ProPhenol Catalysts: Development and Synthetic Applications. Angewandte Chemie (International ed. in English) Trost, B. M., Hung, C. J., Mata, G. 2019

    Abstract

    The ProPhenol ligand is a member of the chiral azacrown family that spontaneously forms a bimetallic complex upon treatment with alkyl metal reagents, such as Et2Zn and Bu2Mg. The resulting complex features Lewis acidic and Bronsted basic sites, enabling simultaneous activation of both nucleophile and electrophile in the same chiral environment. Since the initial report in 2000, metal-ProPhenol catalysts have been used to facilitate a broad range of asymmetric transformations, including aldol, Mannich, and Henry reactions, as well as alkynylations and conjugation additions. By promoting such a diverse array of reactions, these complexes provide rapid and atom-economical access to valuable complex building blocks. In this review, we describe in detail the development and synthetic applications of these versatile catalysts with a special focus on recent efforts to improve reactivity and selectivity through ligand design and structural modification.

    View details for DOI 10.1002/anie.201909692

    View details for PubMedID 31452294

  • New Catalytic Asymmetric Formation of Oxygen Heterocycles Bearing Nucleoside Bases at the Anomeric Carbon. Journal of the American Chemical Society Trost, B. M., Xu, S., Sharif, E. U. 2019

    Abstract

    Pyrimidine nucleosides are an important class of compounds with versatile applications across many fields, including biology and medicinal chemistry. Synthesis of nucleoside analogs in optically pure form via traditional glycosylation has always been a challenge, especially for unnatural carbohydrate motifs which do not have C2 substitution to dictate the stereochemical outcome of the newly formed glyosidic bond. Herein, we report an asymmetric Pd-catalyzed synthesis of nucleoside analogs enabled by the development of a series of chiral ligands. A variety of 5-substituted pyrimidine nucleobases, ranging from 5- to 12-membered ring nucleoside analogs, are generated in excellent yield (up to 96%) as well as diastereo- (>20:1) and enantioselectivity (up to 99.5% ee). These nucleoside analogs bearing an iodide functional group handle allow for rapid transformation to a variety of other interesting pyrimidine nucleoside structures.

    View details for DOI 10.1021/jacs.9b06050

    View details for PubMedID 31194521

  • Chemo-, Regio-, Diastereo-, and Enantioselective Palladium Allylic Alkylation of 1,3-Dioxaboroles as Synthetic Equivalents of alpha-Hydroxyketones. Journal of the American Chemical Society Trost, B. M., Schultz, J. E., Chang, T., Maduabum, M. R. 2019

    Abstract

    We describe the development of a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) of acyclic alpha-hydroxyketones using boronic acids as traceless templates. Condensation of boronic acids with hydroxyketones generates 1,3-dioxaboroles, which can be used directly as pronucleophiles in Pd-AAA reactions. This strategy enables control of the enolate geometry, while removing the issue of O-alkylation. Allylic alcohols can be directly ionized in the presence of Pd(0) and chiral ligands to afford alkylation products with regio- and enantioselectivity. Additionally, a dynamic kinetic asymmetric transformation of allenyl electrophiles affords C-alkylation products in high regio-, diastereo-, and enantioselectivity. To the best of our knowledge, this method represents the first example in Pd-AAA for setting point chirality on a nucleophile simultaneous to stereoinduction on an axial chiral allene.

    View details for DOI 10.1021/jacs.9b04658

    View details for PubMedID 31180647

  • Catalytic (3+2) Palladium-Aminoallyl Cycloaddition with Conjugated Dienes ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Huang, Z. 2019; 58 (19): 6396–99
  • Catalytic (3+2) Palladium-Aminoallyl Cycloaddition with Conjugated Dienes. Angewandte Chemie (International ed. in English) Trost, B. M., Huang, Z. 2019

    Abstract

    We describe the design and application of tailored aminoallyl precursors for catalytic (3+2) cycloaddition with conjugated dienes via a Pd-aminoallyl intermediate. The new cycloaddition reactions override the conventional (4+3) selectivity of aminoallyl cation cycloaddition through a sequence of Pd-allyl transfer and ring closure. A variety of highly substituted or fused pyrrolidine rings were synthesized using the cycloaddition, and can further undergo [1,3] N-to-C rearrangement to five-membered carbocycles with a different palladium catalyst. The utility of the (3+2) cycloaddition is also demonstrated by the preparation of various derivatives from the bicyclic pyrrolidine products.

    View details for PubMedID 30946506

  • Enantioselective Divergent Synthesis of C19-Oxo Eburnane Alkaloids via Palladium-Catalyzed Asymmetric Allylic Alkylation of an N-Alkyl-alpha,beta-unsaturated Lactam JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Bai, Y., Bai, W., Schultz, J. E. 2019; 141 (12): 4811–14
  • Synthesis of Chiral, Densely Substituted Pyrrolidones via Phosphine-Catalyzed Cycloisomerization ORGANIC LETTERS Trost, B. M., Gnanamani, E., Hung, C., Kalnmals, C. A. 2019; 21 (6): 1890–94
  • Enantioselective Divergent Synthesis of C19-Oxo Eburnane Alkaloids via Palladium-Catalyzed Asymmetric Allylic Alkylation of an N-Alkyl-alpha,beta-unsaturated Lactam. Journal of the American Chemical Society Trost, B. M., Bai, Y., Bai, W., Schultz, J. E. 2019

    Abstract

    The C19-oxo-functionalized eburnane alkaloids display unique chemical structure and interesting biological activity. Herein, we report a divergent enantioselective strategy to access these alkaloids by use of a challenging palladium-catalyzed asymmetric allylic alkylation of an N-alkyl-alpha,beta-unsaturated lactam. 19-( S)-OH-Delta14-vincamone (phutdonginin), (-)-19-OH-eburnamine, (+)-19-oxoeburnamine, and (+)-19-OH-eburnamonine (1-4) have been concisely synthesized for the first time in 11 to 13 steps.

    View details for PubMedID 30848892

  • Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Dihydroquinolinones ORGANIC LETTERS Trost, B. M., Nagaraju, A., Wang, F., Zuo, Z., Xu, J., Hull, K. L. 2019; 21 (6): 1784–88
  • Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Dihydroquinolinones. Organic letters Trost, B. M., Nagaraju, A., Wang, F., Zuo, Z., Xu, J., Hull, K. L. 2019

    Abstract

    A palladium-catalyzed decarboxylative asymmetric allylic alkylation (Pd-DAAA) of benzo-fused and non-benzo-fused delta-valerolactams is disclosed. This methodology gives access to chiral lactams bearing C3-quaternary stereocenters, which are central to many natural products and biologically active compounds. The reaction proceeds via palladium-catalyzed ionization of an allyl ester, followed by carbon dioxide extrusion and recombination of the electrophilic Pd-pi-allyl complex with the in situ generated lactam enolate. This final step converts racemic allylic ester starting materials into enantiomerically enriched substituted lactams with high yield and enantiomeric excess.

    View details for PubMedID 30834753

  • Synthesis of Chiral, Densely Substituted Pyrrolidones via Phosphine-Catalyzed Cycloisomerization. Organic letters Trost, B. M., Gnanamani, E., Hung, C. J., Kalnmals, C. A. 2019

    Abstract

    Densely substituted chiral pyrrolidones are synthesized via phosphine-catalyzed cycloisomerization of enantioenriched beta-amino ynones, which are prepared in a single step using a highly enantioselective Zn-ProPhenol-catalyzed Mannich reaction. The exocyclic alkenes in the cyclization products provide versatile handles for further transformations and typically form with good E/ Z selectivity. This cycloisomerization method can be performed in streamlined fashion, without purification of the intermediate Mannich adduct, and extends to anthranilic acid based scaffolds in addition to ProPhenol-derived Mannich adducts.

    View details for PubMedID 30829494

  • Vanadium-Catalyzed Coupling of Allenols with Electrophilic Halide Sources for the Formation of alpha-Halo-alpha ',beta '-unsaturated Ketones ORGANIC LETTERS Trost, B. M., Tracy, J. S., Yusoontorn, T. 2019; 21 (4): 1207–11
  • Vanadium-Catalyzed Synthesis of Geometrically Defined Acyclic Tri- and Tetrasubstituted Olefins from Propargyl Alcohols ACS CATALYSIS Trost, B. M., Tracy, J. S. 2019; 9 (2): 1584–94
  • Tuning the Reactivity of Ketones through Unsaturation: Construction of Cyclic and Acyclic Quaternary Stereocenters via Zn-ProPhenol Catalyzed Mannich Reactions ACS CATALYSIS Trost, B. M., Hung, C., Gnanamani, E. 2019; 9 (2): 1549–57
  • Vanadium-Catalyzed Coupling of Allenols with Electrophilic Halide Sources for the Formation of alpha-Halo-alpha',beta'-unsaturated Ketones. Organic letters Trost, B. M., Tracy, J. S., Yusoontorn, T. 2019

    Abstract

    A vanadium-catalyzed coupling of allenylic alcohols with electrophilic halide sources to form alpha-halo-alpha',beta'-unsaturated ketones is described. The process proceeds through a metal enolate formed from the 1,3-transposition of an allenol that is initiated by a cheap and earth-abundant vanadium oxo catalyst. Fluorine, chlorine, and bromine electrophiles can be utilized, and the resulting products can give rise to the introduction of nitrogen, oxygen, sulfur, and iodine nucleophiles alpha to the ketone through substitution chemistry.

    View details for PubMedID 30689391

  • Elaborating Complex Heteroaryl Containing Cycles via Enantioselective Palladium-Catalyzed Cycloadditions. Angewandte Chemie (International ed. in English) Trost, B. M., Jiao, Z., Hung, C. J. 2019

    Abstract

    A general method for asymmetric synthesis of heteroaryl containing cycles via palladium-catalyzed cyclization is reported. Most classes of nitrogen-containing aromatics, including pyridines, quinolines, pyrimidines, various azoles and the derivatives of nucleobases are compatible substrates, offering various heteroaryl-substituted cyclopentane, pyrrolidine, furanidine and bicyclo [4, 3, 1] decadiene derivatives with good to excellent enantioselectivity and diastereoselectivity.

    View details for DOI 10.1002/anie.201910061

    View details for PubMedID 31483926

  • Palladium-Catalyzed Asymmetric Allylic Alkylation Strategies for the Synthesis of Acyclic Tetrasubstituted Stereocenters SYNTHESIS-STUTTGART Trost, B. M., Schultz, J. E. 2019; 51 (1): 1–30
  • Direct Enantio- and Diastereoselective Vinylogous Addition of Butenolides to Chromones Catalyzed by Zn-ProPhenol. Journal of the American Chemical Society Trost, B. M., Gnanamani, E., Kalnmals, C. A., Hung, C. J., Tracy, J. S. 2019; 141 (4): 1489–93

    Abstract

    We report the first enantio- and diastereoselective 1,4-addition of butenolides to chromones. Both α,β- and β,γ-butenolide nucleophiles are compatible with the Zn-ProPhenol catalyst, and preactivation as the siloxyfurans is not required. The scope of electrophiles includes a variety of substituted chromones, as well as a thiochromone and a quinolone, and the resulting vinylogous addition products are generated in good yield (31 to 98%), diastereo- (3:1 to >30:1), and enantioselectivity (90:10 to 99:1 er). These Michael adducts allow rapid access to several natural product analogs, and can be easily transformed into a variety of other interesting scaffolds as well.

    View details for PubMedID 30642168

  • Development of a Chemo- and Enantioselective Pd-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α-Nitroesters. Angewandte Chemie (International ed. in English) Trost, B. M., Schultz, J. E., Bai, Y. 2019

    Abstract

    We describe the development of a Pd-catalyzed decarboxylative asymmetric allylic alkylation of α-nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo- and enantioselective C-alkylation of electronically challenging benzylic nitronates and sterically encumbered 2-allyl esters. Substrates were efficiently accessed in a combinatorial fashion by a cross-Claisen / α-arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for α-tertiary amine synthesis.

    View details for DOI 10.1002/anie.201904034

    View details for PubMedID 31231880

  • Sulfones as Chemical Chameleons: Versatile Synthetic Equivalents of Small Molecule Synthons. Chemistry (Weinheim an der Bergstrasse, Germany) Trost, B. M., Kalnmals, C. A. 2019

    Abstract

    Sulfones are flexible functional groups that can act as nucleophiles, electrophiles, or even radicals. Changing the reaction conditions can completely alter the reactivity of a sulfonyl group, and as a result, molecules bearing multiple sulfones are versatile building blocks. This review highlights the unique ability of 1,1- and 1,2-bis(sulfones) to masquerade as a vast array of reactive synthons - including methane polyanions, vinyl cations, and all-carbon dipoles - that would be difficult or impossible to access directly.

    View details for DOI 10.1002/chem.201902019

    View details for PubMedID 31185136

  • Palladium-Catalyzed Asymmetric Allylic Fluoroalkylation/Trifluoromethylation. Journal of the American Chemical Society Trost, B. M., Gholami, H., Zell, D. 2019; 141 (29): 11446–51

    Abstract

    The first palladium-catalyzed asymmetric allylic trifluoromethylation is disclosed. The methodology evokes a fundamental principle by which the synergistic interplay of a leaving group and its subsequent activation of the nucleophilic trifluoromethyl group enabled the reaction. Allyl fluorides have been shown to be superior precursors for generation of π-allyl complexes, which lead to trifluoromethylated products with high selectivities and functional group tolerance. This study highlights the unique role of a bidentate diamidophosphite ligand class in palladium-catalyzed reactions that allow a challenging transformation to proceed.

    View details for DOI 10.1021/jacs.9b06231

    View details for PubMedID 31280565

  • Direct Enantio- and Diastereoselective Vinylogous Addition of Butenolides to Chromones Catalyzed by Zn-ProPhenol Journal of the American Chemical Society Trost, B. M., Gnanamani, E., Kalnmals, C. A., Hung, C., Tracy, J. S. 2019

    View details for DOI 10.1021/jacs.8b13367

  • Enantioselective Synthesis of des-Epoxy-Amphidinolide N JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Bai, W., Stivala, C. E., Hohn, C., Poock, C., Heinrich, M., Xu, S., Rey, J. 2018; 140 (49): 17316–26

    Abstract

    des-epoxy-Amphidinolide N has been achieved in 21 longest linear and 30 total steps. Relying on concise fragment preparation and judicious protecting-group design, our convergent synthesis features an atom-economical Ru-catalyzed alkene-alkyne coupling as a key stitching strategy. Calculations reveal a hydrogen-bonding bridge within amphidinolide N. Comparisons of 13C NMR chemical shift differences using our synthetic des-epoxy-amphidinolide N reveal that am-phidinolide N and carbenolide I are likely identical.

    View details for PubMedID 30457857

  • Highly Chemoselective Deprotection of the 2,2,2-Trichloroethoxycarbonyl (Troc) Protecting Group. Organic letters Trost, B. M., Kalnmals, C. A., Tracy, J. S., Bai, W. 2018

    Abstract

    Nonreducing, pH-neutral conditions for the selective cleavage of the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group are reported. Using trimethyltin hydroxide in 1,2-dichloroethane, Troc-protected alcohols, thiols, and amines can be selectively unmasked in the presence of various functionalities that are incompatible with the reducing conditions traditionally used to remove the Troc group. This mild deprotection protocol tolerates a variety of other hydrolytically sensitive and acid/base-sensitive moieties as well.

    View details for PubMedID 30511873

  • Propene as an Atom-Economical Linchpin for Concise Total Synthesis of Polyenes: Piericidin A. Journal of the American Chemical Society Trost, B. M., Gholami, H. 2018

    Abstract

    A concise and convergent total synthesis of piericidin A is disclosed. The synthesis hinges on the utilization of propene as a synthetic linchpin to merge the properly elaborated alkyne fragments, leading to the 1,3,6-triene motif of piericidin A. Utilization of propene as a unique alkene, capable of sequential coupling with two alkynes, is further illustrated in the context of various 1,3,6-triene products. The latter process proceeds with high atom economy and efficiently gives rise to complex frameworks from readily accessible alkyne substrates. This strategic C-C bond formation offers an orthogonal paradigm in the design of synthetic routes, leading to higher step economy and more efficient syntheses of polyunsaturated natural products.

    View details for PubMedID 30173519

  • Enantio- and Diastereoselective Synthesis of Chiral Allenes by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition Reactions. Angewandte Chemie (International ed. in English) Trost, B. M., Zell, D., Mata, G., Hohn, C., Maruniak, A. 2018

    Abstract

    A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium-catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio-, enantio-, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.

    View details for PubMedID 30073727

  • Enantioselective Palladium-Catalyzed [3+2] Cycloaddition of Trimethylenemethane and Fluorinated Ketones. Angewandte Chemie (International ed. in English) Trost, B. M., Mata, G. 2018

    Abstract

    A nitrile-substituted trimethylenemethane (TMM) donor undergoes palladium-catalyzed [3+2] cycloadditions with fluorinated ketones to generate tetrasubsituted trifluoromethylated centers in high enantioselectivity under mild conditions. The carbonate-substituted TMM donor was generated via a self-deprotonation strategy which shows remarkable improvements in regiocontrol, efficiency and atom economy of asymmetric [3+2] cycloadditions. Moreover, the versatility of the nitrile group provides a direct access to a variety of synthetically useful intermediates including amide, aldehyde and ester. The developed reaction conditions allow the synthesis of a wide variety of aromatic, heteroaromatic and aliphatic fluorinated dihydrofurans in excellent regio- and enantioselectivities.

    View details for PubMedID 30071149

  • Direct Catalytic Asymmetric Vinylogous Additions of alpha,beta- and beta,gamma-Butenolides to Polyfluorinated Alkynyl Ketimines. Angewandte Chemie (International ed. in English) Trost, B. M., Hung, C., Scharf, M. 2018

    Abstract

    We report a Zn-ProPhenol catalyzed asymmetric Mannich reaction between butenolides and polyfluorinated alkynyl ketimines to obtain vinylogous products featuring two contiguous tetrasubstituted stereogenic centers. Notably, this is the first successful use of ketimines in the ProPhenol Mannich process, and the reaction offers a new approach for the preparation of pharmaceutically relevant products possessing trifluoromethylated tetrasubstituted alkylamines. The reaction can be performed on large scale with reduced catalyst loading without impacting its efficiency. Moreover, the acetylene moiety can be further elaborated using various methods.

    View details for PubMedID 29969528

  • Branched aldehydes as linchpins for the enantioselective and stereodivergent synthesis of 1,3-aminoalcohols featuring a quaternary stereocentre NATURE CATALYSIS Trost, B. M., Hung, C., Saget, T., Gnanamani, E. 2018; 1 (7): 523–30
  • Synthesis of the Aminocyclitol Core of Jogyamycin via an Enantioselective Pd-Catalyzed Trimethylenemethane (TMM) Cycloaddition. Organic letters Trost, B. M., Zhang, L., Lam, T. M. 2018

    Abstract

    The use of beta-nitroenamines as a new class of acceptors in the enantioselective Pd-catalyzed trimethylenemethane cycloaddition afforded differentiated 1,2-dinitrogen bearing cyclopentanes with three contiguous stereocenters. The utility of these acceptors was demonstrated with the efficient construction of the core of jogyamycin and aminocyclopentitols. Further elaboration of the cycloadducts provided a concise synthetic approach toward joygamycin.

    View details for PubMedID 29939033

  • A Deprotonation Approach to the Unprecedented Amino-Trimethylenemethane Chemistry: Regio-, Diastereo-, and Enantioselective Synthesis of Complex Amino Cycles. Angewandte Chemie (International ed. in English) Trost, B. M., Wang, Y. 2018

    Abstract

    Here we report the first realization of the amino-trimethylenemethane chemistry. The approach employs a deprotonation strategy which simplified the synthesis of the amino- trimethylenemethane donor, requiring only two steps from commercial and inexpensive materials. A broad scope of cycloaddition acceptors (seven different classes) participated in the chemistry, chemo-, regio-, diastereo-, and enantioselectively, generating various types of highly valuable complex amino cycles. Multiple derivatization reactions that further elaborated the initial amino cycles were performed in one pot. Ultimately, we applied the amino-trimethylenemethane chemistry to synthesize a potential pharmaceutical in 8 linear steps and 7.5% overall yield, which previously was achieved in 18 linear steps and 0.6% overall yield.

    View details for PubMedID 29924916

  • Direct catalytic enantioselective amination of ketones for the formation of tri- and tetrasubstituted stereocenters CHEMICAL SCIENCE Trost, B. M., Tracy, J. S., Saget, T. 2018; 9 (11): 2975–80

    Abstract

    Herein, we report a Zn-ProPhenol catalyzed direct asymmetric amination reaction of unactivated aryl and vinyl ketones using di-tert-butyl azodicarboxylate as a cheap and practical electrophilic nitrogen source. Importantly, this methodology works with both α-branched and unbranched ketones for the construction of tri- and tetrasubstituted N-containing stereocenters. The reaction can be run at gram-scale with low catalyst loadings and features a recoverable and reusable ligand. Finally, the enantioenriched hydrazine products can be readily converted into versatile building blocks such as α-amino carbonyl compounds and β-amino alcohols.

    View details for PubMedID 29719678

    View details for PubMedCentralID PMC5897889

  • Organic Synthesis. Use of Alkynes as a Key to Innovation in Designing Structure for Function ISRAEL JOURNAL OF CHEMISTRY Trost, B. M., Tracy, J. S. 2018; 58 (1-2): 18–27
  • Sulfones as Synthetic Linchpins: Transition Metal-Free sp3-sp2 and sp2-sp2 Cross-Couplings Between Geminal bis(Sulfones) and Organolithium Compounds. Chemistry (Weinheim an der Bergstrasse, Germany) Trost, B. M., Kalnmals, C. 2018

    Abstract

    Herein, we report a valuable umpolung strategy that highlights the ambiphilic nature of the bis(phenylsulfonyl)methyl synthon and demonstrates its utility as a synthetic linchpin. While the bis(phenylsulfonyl)methyl group is typically introduced as an sp3 carbon nucleophile, we demonstrate that it can also function as an effective sp2 carbon electrophile in the presence of organolithium nucleophiles. Akyl- and aryllithiums couple with the central carbon of the bis(phenylsulfonyl)methyl unit to ultimately generate trisubstituted alkenes, comprising a formal sp3-sp2 and sp2-sp2 cross-coupling between organolithiums and bis(sulfones). This process occurs almost instantaneously at -78 °C in the absence of any transition metals. By developing this curious transformation, we demonstrate that bis(phenylsulfonyl)methane is a valuable synthetic linchpin that can undergo two C-C bond formations as an sp3 nucleophile, followed by a third C-C bond forming reaction as an effective sp2 electrophile. This discovery significantly enhances the utility of this ubiquitous - but underutilized - linker group.

    View details for PubMedID 29543985

  • Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes. Journal of the American Chemical Society Trost, B. M., Bai, W., Hohn, C., Bai, Y., Cregg, J. J. 2018; 140 (21): 6710–17

    Abstract

    Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

    View details for PubMedID 29750514

  • Catalytic palladium-oxyallyl cycloaddition. Science (New York, N.Y.) Trost, B. M., Huang, Z., Murhade, G. M. 2018; 362 (6414): 564–68

    Abstract

    Exploration of intermediates that enable chemoselective cycloaddition reactions and expeditious construction of fused- or bridged-ring systems is a continuous challenge for organic synthesis. As an intermediate of interest, the oxyallyl cation has been harnessed to synthesize architectures containing seven-membered rings via (4+3) cycloaddition. However, its potential to access five-membered skeletons is underdeveloped, largely due to the thermally forbidden (3+2) pathway. Here, the combination of a tailored precursor and a Pd(0) catalyst generates a Pd-oxyallyl intermediate that cyclizes with conjugated dienes to produce a diverse array of tetrahydrofuran skeletons. The cycloaddition overrides conventional (4+3) selectivity by proceeding through a stepwise pathway involving a Pd-allyl transfer and ring closure sequence. Subsequent treatment of the (3+2) adducts with a palladium catalyst converts the heterocycles to the carbocyclic cyclopentanones.

    View details for PubMedID 30385573

  • Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between alpha,beta- and beta,gamma-Butenolides and Aldimines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Gnanamani, E., Tracy, J. S., Kalnmals, C. A. 2017; 139 (50): 18198–201
  • Pd-catalyzed asymmetric allylic alkylations via C-H activation of N-allyl imines with glycinates CHEMICAL SCIENCE Trost, B. M., Li, X. 2017; 8 (10): 6815–21

    Abstract

    Herein is reported the first example of palladium-catalyzed asymmetric allylic alkylation (AAA) reactions involving 2-aza-π-allyl palladium intermediates. The 2-aza-π-allyl complex was generated via a novel mode of activation of N-allyl imines. Pd-catalyzed C(sp3)-H activation of N-allyl imines and subsequent nucleophilic attack by glycinates delivered vicinal diamino derivatives as the sole regioisomers with high levels of diastereo- and enantio-control in the presence of the chiral, bidentate (S,S)-Cy-DIOP ligand. This procedure is highly atom economical and could also be performed by a simple one-pot operation starting from aldehydes, allyl amines and glycinates under mild conditions. The products of this transformation could be converted into various useful derivatives, where the allyl substitution serves as a unique tool for differentiating the two amino moieties in the products.

    View details for PubMedID 29147506

    View details for PubMedCentralID PMC5643980

  • Controlling Regioselectivity in the Enantioselective N-Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc-ProPhenol. Angewandte Chemie (International ed. in English) Trost, B. M., Gnanamani, E., Hung, C. J. 2017; 56 (35): 10451–56

    Abstract

    The enantioselective N-alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc-ProPhenol dinuclear complex under mild conditions to afford N-alkylated indole derivatives in good yield (up to 86%) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N-alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N-alkylation products will open new windows for asymmetric catalysis and medicinal chemistry.

    View details for PubMedID 28654735

  • Carbon-Nitrogen Bond Formation via the Vanadium Oxo Catalyzed Sigmatropic Functionalization of Allenols. Organic letters Trost, B. M., Tracy, J. S. 2017; 19 (10): 2630-2633

    Abstract

    A vanadium catalyzed 1,3-rearrangement of allenols to form transient vanadium enolates that selectively couple with electrophilic nitrogen sources is reported even in the presence of competing simple protonation and Alder-ene pathways. Hydrazine products can be cyclized in a 6-endo-trig fashion which, upon reductive cleavage of the N-N bond, yield 1,4-diamines. Additionally, cleavage of the N-N bond before cyclization can be achieved to form β-hydroxy amines, a common structural motif of biologically active compounds.

    View details for DOI 10.1021/acs.orglett.7b00961

    View details for PubMedID 28467706

  • Stereoselective Synthesis of Exocyclic Tetrasubstituted Vinyl Halides via Ru-Catalyzed Halotropic Cycloisomerization of 1,6-Haloenynes ORGANIC LETTERS Trost, B. M., Kalnmals, C. A. 2017; 19 (9): 2346-2349

    Abstract

    Herein, a ruthenium-catalyzed cycloisomerization that transforms 1,6-haloenynes into 5-membered carbo- and heterocycles that bear exocyclic, stereodefined, tetrasubstituted vinyl halides is reported. The reaction is insensitive to air and water, tolerates a variety of functional groups, and proceeds with good to excellent stereoselectivity and yield.

    View details for DOI 10.1021/acs.orglett.7b00879

    View details for Web of Science ID 000401044500038

    View details for PubMedID 28436669

  • Isomerization of N-Allyl Amides To Form Geometrically Defined Di-, Tri-, and Tetrasubstituted Enamides JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Cregg, J. J., Quach, N. 2017; 139 (14): 5133-5139

    Abstract

    Enamides represent bioactive pharmacophores in various natural products, and have become increasingly common reagents for asymmetric incorporation of nitrogen functionality. Yet the synthesis of the requisite geometrically defined enamides remains problematic, especially for highly substituted and Z-enamides. Herein we wish to report a general atom economic method for the isomerization of a broad range of N-allyl amides to form Z-di-, tri-, and tetrasubstituted enamides with exceptional geometric selectivity. This report represents the first examples of a catalytic isomerization of N-allyl amides to form nonpropenyl disubstituted, tri- and tetrasubstituted enamides with excellent geometric control. Applications of these geometrically defined enamides toward the synthesis of cis vicinal amino alcohols and tetrasubstituted α-borylamido complexes are discussed.

    View details for DOI 10.1021/jacs.7b00564

    View details for Web of Science ID 000399353800028

    View details for PubMedID 28252296

  • Development of the Regiodivergent Asymmetric Prenylation of 3-Substituted Oxindoles CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Chan, W. H., Malhotra, S. 2017; 23 (18): 4405-4414

    Abstract

    This paper describes our efforts to design a Pd-catalyzed asymmetric prenylation of 3-substituted oxindoles that affords access to both the linear and reverse-prenylated products. Both 3-alkyl- and 3-aryloxindoles performed well under our optimized reaction conditions. The regiodivergent alkylation of monoterpene-derived electrophiles using this methodology was also investigated. The utility of this methodology in natural product synthesis was demonstrated through the efficient total syntheses of four Flustra alkaloids, which also allowed the absolute stereochemistry of the prenylated oxindole products to be assigned. Surprisingly, the same enantiomer of ligand produced linear and branched regioisomers of opposite chirality.

    View details for DOI 10.1002/chem.201605810

    View details for Web of Science ID 000399314800022

    View details for PubMedID 28141896

  • Indenylmetal Catalysis in Organic Synthesis. Angewandte Chemie (International ed. in English) Trost, B. M., Ryan, M. C. 2017; 56 (11): 2862-2879

    Abstract

    Synthetic organic chemists have a long-standing appreciation for transition metal cyclopentadienyl complexes, of which many have been used as catalysts for organic transformations. Much less well known are the contributions of the benzo-fused relative of the cyclopentadienyl ligand, the indenyl ligand, whose unique properties have in many cases imparted differential reactivity in catalytic processes toward the synthesis of small molecules. In this Review, we present examples of indenylmetal complexes in catalysis and compare their reactivity to their cyclopentadienyl analogues, wherever possible.

    View details for DOI 10.1002/anie.201609054

    View details for PubMedID 27806434

  • Indenylmetal Catalysis in Organic Synthesis ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Ryan, M. C. 2017; 56 (11): 2862-2879

    Abstract

    Synthetic organic chemists have a long-standing appreciation for transition metal cyclopentadienyl complexes, of which many have been used as catalysts for organic transformations. Much less well known are the contributions of the benzo-fused relative of the cyclopentadienyl ligand, the indenyl ligand, whose unique properties have in many cases imparted differential reactivity in catalytic processes toward the synthesis of small molecules. In this Review, we present examples of indenylmetal complexes in catalysis and compare their reactivity to their cyclopentadienyl analogues, wherever possible.

    View details for DOI 10.1002/anie.201609054

    View details for Web of Science ID 000397307600005

  • Efficient Access to Chiral Trisubstituted Aziridines via Catalytic Enantioselective Aza-Darzens Reactions. Angewandte Chemie (International ed. in English) Trost, B. M., Saget, T., Hung, C. J. 2017; 56 (9): 2440-2444

    Abstract

    Herein, we report a Zn-ProPhenol catalyzed aza-Darzens reaction using chlorinated aromatic ketones as nucleophilic partners for the efficient and enantioselective construction of complex trisubstituted aziridines. The α-chloro-β-aminoketone intermediates featuring a chlorinated tetrasubstituted stereocenter can be isolated in high yields and selectivities for further derivatization. Alternatively, they can be directly transformed to the corresponding aziridines in a one-pot fashion. Of note, the reaction can be run on gram-scale with low catalyst loading without impacting its efficiency. Moreover, this methodology was extended to α-bromoketones which are scarcely used in enantioselective catalysis because of their sensitivity and lack of accessibility.

    View details for DOI 10.1002/anie.201607845

    View details for PubMedID 28111864

  • Ru-catalyzed sequence for the synthesis of cyclic amido-ethers CHEMICAL SCIENCE Trost, B. M., Sharif, E. U., Cregg, J. J. 2017; 8 (1): 770-774

    View details for DOI 10.1039/c6sc02849g

    View details for Web of Science ID 000391454500095

  • Ru-catalyzed sequence for the synthesis of cyclic amido-ethers. Chemical science Trost, B. M., Sharif, E. U., Cregg, J. J. 2017; 8 (1): 770–74

    Abstract

    Efficient synthesis of versatile building blocks for enabling medicinal chemistry research has always challenged synthetic chemists to develop innovative methods. Of particular interest are the methods that are amenable to the synthesis of chemically distinct and diverse classes of pharmaceutically relevant motifs. Herein we report a general method for the one-pot synthesis of cyclic α-amido-ethers containing different amide functionalities including lactams, tetramic acids and amino acids. For the incorporation of the nucleotide bases, a chemo and regioselective palladium-catalyzed transformation has been developed, providing rapid access to nucleoside analogs.

    View details for PubMedID 28451225

  • Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines. Journal of the American Chemical Society Trost, B. M., Gnanamani, E., Tracy, J. S., Kalnmals, C. A. 2017; 139 (50): 18198–201

    Abstract

    We report a Zn-ProPhenol catalyzed reaction between butenolides and imines to obtain tetrasubstituted vinylogous Mannich products in good yield and diastereoselectivity with excellent enantioselectivity (97 to >99.5% ee). Notably, both α,β- and β,γ-butenolides can be utilized as nucleophiles in this transformation. The imine partner bears the synthetically versatile N-Cbz group, avoiding the use of the specialized aryl directing groups previously required in related work. Additionally, the reaction can be performed on gram scale with reduced catalyst loading as low as 2 mol %. The functional group-rich products can be further elaborated using a variety of methods.

    View details for PubMedID 29198100

  • Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products CHEMICAL REVIEWS Trost, B. M., Knopf, J. D., Brindle, C. S. 2016; 116 (24): 15035-15088

    Abstract

    Fostriecin and related natural products present a significant challenge for synthetic chemists due to their structural complexity and chemical sensitivity. This review will chronicle the successful efforts of synthetic chemists in the construction of these biologically active molecules. Key carbon-carbon bond forming reactions will be highlighted, as well as the methods used to install the numerous stereocenters present in this class of compounds.

    View details for DOI 10.1021/acs.chemrev.6b00488

    View details for Web of Science ID 000391081900003

    View details for PubMedID 28027648

  • Synthesis of a 1,3-Bridged Macrobicyclic Enyne via Chemoselective Cycloisomerization Using Palladium-Catalyzed Alkyne-Alkyne Coupling JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Masters, J. T., Le Valliant, F., Lumb, J. 2016; 81 (20): 10023-10028

    Abstract

    A unique intramolecular Pd-catalyzed alkyne-alkyne coupling is presented. This transformation generates a strained, 1,3-bridged, macrocyclic enyne. The process was readily executed on gram scale, and the structure of the product was elucidated via X-ray crystallographic analysis. A mechanistic rationale for the observed chemoselectivity is provided.

    View details for DOI 10.1021/acs.joc.6b01920

    View details for Web of Science ID 000386187500054

  • Synthesis of a 1,3-Bridged Macrobicyclic Enyne via Chemoselective Cycloisomerization Using Palladium-Catalyzed Alkyne-Alkyne Coupling. journal of organic chemistry Trost, B. M., Masters, J. T., Le Vaillant, F., Lumb, J. 2016: -?

    Abstract

    A unique intramolecular Pd-catalyzed alkyne-alkyne coupling is presented. This transformation generates a strained, 1,3-bridged, macrocyclic enyne. The process was readily executed on gram scale, and the structure of the product was elucidated via X-ray crystallographic analysis. A mechanistic rationale for the observed chemoselectivity is provided.

    View details for PubMedID 27648602

  • sequential palladium and copper catalysis. Chemical science Trost, B. M., Masters, J. T., Taft, B. R., Lumb, J. 2016; 7 (9): 6217-6231

    Abstract

    We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regio- and enantioselective copper-catalyzed conjugate reduction. The process exhibits a high functional group tolerance, and this enables the synthesis of a broad range of chiral products from simple, readily available alkyne precursors. The utility of the method is demonstrated through the elaboration of the chiral β-alkynyl products into a variety of different molecular scaffolds. Its value in complex molecule synthesis is further validated through a concise, enantioselective synthesis of AMG 837, a potent GPR40 receptor agonist.

    View details for PubMedID 27746892

  • Total Synthesis of (-)-Lasonolide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Stivala, C. E., Fandrick, D. R., Hull, K. L., Huang, A., Poock, C., Kalkofen, R. 2016; 138 (36): 11690-11701

    Abstract

    The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our first-generation approach to the formal synthesis of lasonolide A. The key findings from these studies ultimately allowed us to go on and complete a total synthesis of lasonolide A. The convergent approach unites two highly complex fragments utilizing a Ru-catalyzed alkene-alkyne coupling. This type of coupling typically generates branched products; however, through a detailed investigation, we are now able to demonstrate that subtle structural changes to the substrates can alter the selectivity to favor the formation of the linear product. The synthesis of the fragments features a number of atom-economical transformations which are highlighted by the discovery of an engineered enzyme to perform a dynamic kinetic reduction of a β-ketoester to establish the absolute stereochemistry of the southern tetrahydropyran ring with high levels of enantioselectivity.

    View details for DOI 10.1021/jacs.6b05127

    View details for Web of Science ID 000383410700042

    View details for PubMedID 27548113

  • Development of a Coordinatively Unsaturated Chiral Indenylruthenium Catalyst ORGANIC LETTERS Trost, B. M., Ryan, M. C., Maurer, D. 2016; 18 (13): 3166-3169

    Abstract

    An unprecedented coordinatively unsaturated chiral indenylruthenium complex 12 was designed and synthesized to provide additional coordination sites for Ru-catalyzed asymmetric transformations. In an attempt to catalyze an asymmetric enyne cycloisomerization reaction of 1,6-enyne, significant amounts of hydroxycyclization were observed. Up to 84:16 er of the hydroxycyclization product was obtained in 2-MeTHF. This chiral indenylruthenium catalyst could also perform an asymmetric redox isomerization/C-H insertion reaction in up to 90:10 er.

    View details for DOI 10.1021/acs.orglett.6b01375

    View details for Web of Science ID 000379455300032

    View details for PubMedID 27333303

  • Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Ryan, M. C., Rao, M. 2016; 12: 1136-1152

    Abstract

    A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent.

    View details for DOI 10.3762/bjoc.12.110

    View details for Web of Science ID 000377239300001

    View details for PubMedCentralID PMC4979649

  • Direct Catalytic Asymmetric Mannich Reactions for the Construction of Quaternary Carbon Stereocenters. Journal of the American Chemical Society Trost, B. M., Saget, T., Hung, C. J. 2016; 138 (11): 3659-3662

    Abstract

    Herein, we report a Zn-ProPhenol catalyzed Mannich reaction using α-branched ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of quaternary carbon stereocenters. The reaction can be run on a gram-scale with a low catalyst loading without impacting its efficiency. Moreover, the Mannich adducts can be further elaborated with complete diastereocontrol to access molecules possessing complex stereotriads.

    View details for DOI 10.1021/jacs.6b01187

    View details for PubMedID 26952276

    View details for PubMedCentralID PMC4866641

  • Direct Catalytic Asymmetric Mannich Reactions for the Construction of Quaternary Carbon Stereocenters JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Saget, T., Hung, C. (. 2016; 138 (11): 3659-3662
  • A Ruthenium/Phosphoramidite-Catalyzed Asymmetric Interrupted Metallo-ene Reaction. Journal of the American Chemical Society Trost, B. M., Ryan, M. C. 2016; 138 (9): 2981-2984

    Abstract

    Allylic chlorides prepared from commercially available trans-1,4-dichloro-2-butene were converted to trans-disubstituted 5- and 6-membered ring systems with perfect diastereoselectivity and high enantioselectivity under chiral ruthenium catalysis. These products contain stereodefined secondary and tertiary alcohols that originate from the trapping of an alkylruthenium intermediate with adventitious water. Key to the success of this transformation was the development of a new BINOL-based phosphoramidite ligand containing bulky substitution at its 3- and 3'-positions. As a demonstration of product utility, diastereoselective Friedel-Crafts reactions were performed on the chiral benzylic alcohols in high yield and stereoselectivity.

    View details for DOI 10.1021/jacs.6b00983

    View details for PubMedID 26899551

  • Ruthenium-Catalyzed Multicomponent Reactions: Access to -Silyl--Hydroxy Vinylsilanes, Stereodefined 1,3-Dienes, and Cyclohexenes CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Koester, D. C., Sharif, E. U. 2016; 22 (8): 2634-2638

    Abstract

    The synthesis of densly functionized α-silyl-β-hydroxyl vinylsilanes via ruthenium-catalyzed multicomponent reaction (MCR) is reported herein. Exceptionally high regio- and diastereoselectivity was achieved by employing an unprecedented hydrosilylation of bifunctional silyl-propargyl boronates. The simple protocol, mild reaction conditions, and unique tolerability of this method make it a valuable tool for the synthesis of highly elaborated building blocks. The one-pot synthesis of stereodefined olefins, the generation of a valuable cyclohexene building block through a four-component MCR, and further functionalization in an abundance of diastereoselective reactions is disclosed herein.

    View details for DOI 10.1002/chem.201504981

    View details for Web of Science ID 000370193000014

    View details for PubMedID 26669265

    View details for PubMedCentralID PMC4866645

  • Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral beta-Fluoroamines ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Saget, T., Lerchen, A., Hung, C. (. 2016; 55 (2): 781-784
  • Re-Orienting Coupling of Organocuprates with Propargyl Electrophiles from SN2' to SN2 with Stereocontrol. Chemical science Trost, B. M., Debien, L. 2016; 7 (8): 4985–89

    Abstract

    Diorganocuprate(I) reagents derived from lithiated heterocycles and CuCN react with enantioenriched secondary propagryl bromides to give the corresponding propargylated heterocycles. While propargyl electrophiles typically undergo SN2' displacement, this transformation represents the first example of the reaction of hard carbanions with propargyl eletrophiles in an SN2 fashion and occurs with excellent levels of stereoinversion. The new method was applied to the formal synthesis of (+)-frondosin B.

    View details for PubMedID 28066535

    View details for PubMedCentralID PMC5207346

  • Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral β-Fluoroamines. Angewandte Chemie (International ed. in English) Trost, B. M., Saget, T., Lerchen, A., Hung, C. J. 2016; 55 (2): 781–84

    Abstract

    Reported herein is a Zn/Prophenol-catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of β-fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover, a related aldol reaction was also developed. Together, these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C-F centers.

    View details for PubMedID 26609784

  • Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization. Beilstein journal of organic chemistry Trost, B. M., Ryan, M. C., Rao, M. 2016; 12: 1136–52

    Abstract

    A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent.

    View details for PubMedID 27559366

  • Asymmetric synthesis of chiral beta-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis CHEMICAL SCIENCE Trost, B. M., Masters, J. T., Taft, B. R., Lumb, J. 2016; 7 (9): 6217-6231

    View details for DOI 10.1039/c6sc01724j

    View details for Web of Science ID 000382488500074

    View details for PubMedID 27746892

  • Re-orienting coupling of organocuprates with propargyl electrophiles from S(N)2 ' to S(N)2 with stereocontrol CHEMICAL SCIENCE Trost, B. M., Debien, L. 2016; 7 (8): 4985-4989

    View details for DOI 10.1039/c6sc01086e

    View details for Web of Science ID 000380893900024

  • Transition metal-catalyzed couplings of alkynes to 1,3-enynes: modern methods and synthetic applications CHEMICAL SOCIETY REVIEWS Trost, B. M., Masters, J. T. 2016; 45 (8): 2212-2238

    Abstract

    The metal-catalyzed coupling of alkynes is a powerful method for the preparation of 1,3-enynes, compounds that are of broad interest in organic synthesis. Numerous strategies have been developed for the homo- and cross coupling of alkynes to enynes via transition metal catalysis. In such reactions, a major issue is the control of regio-, stereo-, and, where applicable, chemoselectivity. Herein, we highlight prominent methods for the selective synthesis of these valuable compounds. Further, we illustrate the utility of these processes through specific examples of their application in carbocycle, heterocycle, and natural product syntheses.

    View details for DOI 10.1039/c5cs00892a

    View details for Web of Science ID 000374403800009

    View details for PubMedID 27086769

    View details for PubMedCentralID PMC4837660

  • Broad Spectrum Enolate Equivalent for Catalytic Chemo-, Diastereo-, and Enantioselective Addition to N-Boc Imines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Hung, C. (. 2015; 137 (50): 15940-15946
  • Stereocontrolled Synthesis of Vinyl Boronates and Vinyl Silanes via Atom-Economical Ruthenium-Catalyzed Alkene-Alkyne Coupling ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Koester, D. C., Herron, A. N. 2015; 54 (52): 15863-15866

    Abstract

    The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru-catalyzed alkene-alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron- and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross-coupling reactions, and a Chan-Lam-type allyloxylation followed by a Claisen rearrangement. A sequential one-pot alkene-alkyne-coupling/allylation-sequence with an aldehyde to deliver a highly complex α-silyl-β-hydroxy olefin with a handle for further functionalization was also realized.

    View details for DOI 10.1002/anie.201509238

    View details for Web of Science ID 000368061800042

    View details for PubMedID 26572804

    View details for PubMedCentralID PMC4715692

  • Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Osipov, M. 2015; 21 (46): 16318-16343

    Abstract

    The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed.

    View details for DOI 10.1002/chem.201501735

    View details for Web of Science ID 000365132100005

    View details for PubMedID 26353936

    View details for PubMedCentralID PMC4698125

  • Contemporaneous Dual Catalysis: Aldol Products from Non-Carbonyl Substrates. Chemistry (Weinheim an der Bergstrasse, Germany) Trost, B. M., Tracy, J. S. 2015; 21 (43): 15108-15112

    View details for DOI 10.1002/chem.201502973

    View details for PubMedID 26334442

  • Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the s-Electron-Withdrawing Trifluoromethyl Group. Journal of the American Chemical Society Trost, B. M., Debien, L. 2015; 137 (36): 11606-11609

    Abstract

    α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique σ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism.

    View details for DOI 10.1021/jacs.5b07573

    View details for PubMedID 26291872

  • A Highly Convergent Total Synthesis of Leustroducsin B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Biannic, B., Brindle, C. S., O'Keefe, B. M., Hunter, T. J., Ngai, M. 2015; 137 (36): 11594-11597

    Abstract

    Leustroducsin B exhibits a large variety of biological activities and unique structural features. An efficient and highly convergent total synthesis of Leustroducsin B was achieved in 17 longest linear and 39 total steps by disconnecting the molecule into three fragments having similar levels of complexity. These pieces were connected via a highly efficient chelate-controlled addition of a vinyl zincate to an α-hydroxy ketone and a silicon-mediated cross-coupling. The stereochemistry of the central and western fragments was set catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol reaction and a palladium-catalyzed asymmetric allylic alkylation.

    View details for DOI 10.1021/jacs.5b07438

    View details for Web of Science ID 000361502800014

    View details for PubMedID 26313159

    View details for PubMedCentralID PMC4621997

  • Metal catalyzed allylic alkylation: its development in the Trost laboratories TETRAHEDRON Trost, B. M. 2015; 71 (35): 5708-5733
  • Development of Non-C2-symmetric ProPhenol Ligands. The Asymmetric Vinylation of N-Boc Imines ORGANIC LETTERS Trost, B. M., Hung, C. (., Koester, D. C., Miller, Y. 2015; 17 (15): 3778-3781

    Abstract

    The development and application of a new generation of non-C2-symmetric ProPhenol ligands is reported herein. Rational design of the ProPhenol ligand paved the way to the first catalytic and asymmetric vinylation of N-Boc imines via hydrozirconation giving rise to valuable allylic amines in excellent yields and enantioselectivities. The utility of this method was demonstrated by developing the shortest reported asymmetric synthesis of the selective serotonine reuptake inhibitor (SSRI) (-)-dapoxetine.

    View details for DOI 10.1021/acs.orglett.5b01755

    View details for Web of Science ID 000359393800035

    View details for PubMedID 26200769

  • Palladium-Catalyzed C-H Activation of N-Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza-1,3-Dienes ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Mahapatra, S., Hansen, M. 2015; 54 (20): 6032-6036

    Abstract

    A new mode of activation of an imine via a rare aza-substituted π-allyl complex is described. Palladium-catalyzed C(sp(3))-H activation of the N-allyl imine and the subsequent nucleophilic attack by the α-alkyl cyanoester produced the 1-aza-1,3-diene as the sole regioisomer. In contrast, nucleophilic attack by the α-aryl cyanoester exclusively delivered the 2-aza-1,3-diene, which was employed in an inverse-electron-demand Diels-Alder reaction for heterobiaryl synthesis.

    View details for DOI 10.1002/anie.201501322

    View details for Web of Science ID 000354255400043

    View details for PubMedID 25809660

  • Development of Chiral Sulfoxide Ligands for Asymmetric Catalysis ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Rao, M. 2015; 54 (17): 5026-5043

    Abstract

    Nitrogen-, phosphorus-, and oxygen-based ligands with chiral backbones have been the historic workhorses of asymmetric transition-metal-catalyzed reactions. On the contrary, sulfoxides containing chirality at the sulfur atom have mainly been used as chiral auxiliaries for diastereoselective reactions. Despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination, these compounds have only recently emerged as a versatile class of chiral ligands. In this Review, we detail the history of the development of chiral sulfoxide ligands for asymmetric catalysis. We also provide brief descriptions of metal-sulfoxide bonding and strategies for the synthesis of enantiopure sulfoxides. Finally, insights into the future development of this underutilized ligand class are discussed.

    View details for DOI 10.1002/anie.201411073

    View details for Web of Science ID 000354190800007

    View details for PubMedID 25801825

  • Redox Cycloisomerization Approach to 1,2-Dihydropyridines ORGANIC LETTERS Trost, B. M., Biannic, B. 2015; 17 (6): 1433-1436

    Abstract

    The phosphine-catalyzed synthesis of 1,2-dihydropyridines via an alkyne isomerization/electrocyclization sequence is described. Propargylidenecarbamate substrates were prepared following a one-pot procedure between a terminal alkyne, a benzonitrile, and a chloroformate in the presence of trimethylaluminum. This methodology gives access to a diverse set of 2,6-disubstituted 1,2-dihydropyridines in high yield. The products can be easily converted into substituted piperidines or pyridines, and this methodology was applied to the synthesis of indolizidines.

    View details for DOI 10.1021/acs.orglett.5b00279

    View details for Web of Science ID 000351558100022

    View details for PubMedID 25760318

  • ProPhenol-Catalyzed Asymmetric Additions by Spontaneously Assembled Dinuclear Main Group Metal Complexes ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M., Bartlett, M. J. 2015; 48 (3): 688-701

    Abstract

    The development of catalytic enantioselective transformations has been the focus of many research groups over the past half century and is of paramount importance to the pharmaceutical and agrochemical industries. Since the award of the Nobel Prize in 2001, the field of enantioselective transition metal catalysis has soared to new heights, with the development of more efficient catalysts and new catalytic transformations at increasing frequency. Furthermore, catalytic reactions that allow higher levels of redox- and step-economy are being developed. Thus, alternatives to asymmetric alkene dihydroxylation and the enantioselective reduction of α,β-unsaturated ketones can invoke more strategic C-C bond forming reactions, such as asymmetric aldol reactions of an aldehyde with α-hydroxyketone donors or enantioselective alkynylation of an aldehyde, respectively. To facilitate catalytic enantioselective addition reactions, including the aforementioned aldol and alkynylation reactions, our lab has developed the ProPhenol ligand. In this Account, we describe the development and application of the ProPhenol ligand for asymmetric additions of both carbon- and heteroatom-based nucleophiles to various electrophiles. The ProPhenol ligand spontaneously forms chiral dinuclear metal complexes when treated with an alkyl metal reagent, such as Et2Zn or Bu2Mg. The resulting complex contains both a Lewis acidic site to activate an electrophile and a Brønsted basic site to deprotonate a pronucleophile. Initially, our research focused on the use of Zn-ProPhenol complexes to facilitate the direct aldol reaction. Fine tuning of the reaction through ligand modification and the use of additives enabled the direct aldol reaction to proceed in high yields and stereoselectivities with a broad range of donor substrates, including acetophenones, methyl ynones, methyl vinyl ketone, acetone, α-hydroxy carbonyl compounds, and glycine Schiff bases. Additionally, an analogous magnesium ProPhenol complex was used to facilitate enantioselective diazoacetate aldol reactions with aryl, α,β-unsaturated, and aliphatic aldehydes. The utility of bimetallic ProPhenol catalysts was extended to asymmetric additions with a wide range of substrate combinations. Effective pronucleophiles include oxazolones, 2-furanone, nitroalkanes, pyrroles, 3-hydroxyoxindoles, alkynes, meso-1,3-diols, and dialkyl phosphine oxides. These substrates were found to be effective with a number of electrophiles, including aldehydes, imines, nitroalkenes, acyl silanes, vinyl benzoates, and α,β-unsaturated carbonyls. A truly diverse range of enantioenriched compounds have been prepared using the ProPhenol ligand, and the commercial availability of both ligand enantiomers makes it ideally suited for the synthesis of complex molecules. To date, enantioselective ProPhenol-catalyzed reactions have been used in the synthesis of more than 20 natural products.

    View details for DOI 10.1021/ar500374r

    View details for Web of Science ID 000351326900021

    View details for PubMedID 25650587

    View details for PubMedCentralID PMC4365908

  • A new class of non-c2-symmetric ligands for oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones. Journal of the American Chemical Society Trost, B. M., Donckele, E. J., Thaisrivongs, D. A., Osipov, M., Masters, J. T. 2015; 137 (7): 2776-2784

    Abstract

    We report the discovery, synthesis, and application of a new class of non-C2-symmetric phosphoramidite ligands derived from pyroglutamic acid for use in both oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones. The resulting chiral products are typically obtained in high yield with good to excellent levels of enantioselectivity.

    View details for DOI 10.1021/jacs.5b00786

    View details for PubMedID 25629592

  • Ruthenium-catalyzed alkene-alkyne coupling of disubstituted olefins: application to the stereoselective synthesis of trisubstituted enecarbamates. Journal of the American Chemical Society Trost, B. M., Cregg, J. J. 2015; 137 (2): 620-623

    Abstract

    The Ru-catalyzed alkene-alkyne coupling reaction has been demonstrated to be an enabling methodology for the synthesis of complex molecules. However, to date, it has been limited to monosubstituted olefins. Herein we report the first general utilization of disubstituted olefins in the Ru-catalyzed alkene-alkyne coupling reaction by employing carbamate directing groups. The products are stereodefined trisusbstituted enecarbamates. The elaboration of these structures toward the asymmetric synthesis of complex aminocyclopentitols and 1,2-amino alcohols is discussed.

    View details for DOI 10.1021/ja511911b

    View details for PubMedID 25551414

  • Metal Catalyzed Allylic Alkylation: Its Development in the Trost Laboratories. Tetrahedron Trost, B. M. 2015; 71 (35): 5708–33

    View details for PubMedID 26236048

    View details for PubMedCentralID PMC4517299

  • Broad Spectrum Enolate Equivalent for Catalytic Chemo-, Diastereo-, and Enantioselective Addition to N-Boc Imines. Journal of the American Chemical Society Trost, B. M., Hung, C. J. 2015; 137 (50): 15940–46

    Abstract

    Alkynyl ketones are attractive but challenging nucleophiles in enolate chemistry. Their susceptibility to other reactions such as Michael additions and the difficulty of controlling the enolate geometry make them difficult substrates. Mannich-type reactions, which previously have not been reported using N-carbamoyl-imines with simple ketone enolates, became our objective. In this report, we describe the first direct catalytic Mannich-type reaction between various ynones and N-Boc imines, whose stereocontrol presumably derives from catalyst control of enolate geometry. This method produces α-substituted β-amino ynones with excellent chemo-, diastereo-, and enantioselectivity. The products can be readily transformed into a broad range of molecular scaffolds upon further one-step transformations, demonstrating the utility of ynones as masked synthetic equivalents for a variety of unsymmetrically substituted acyclic ketones. In particular, alkynyl alkyl ketones resolve the long-standing problem of the inability to use the enolates of unsymmetrical dialkyl ketones lacking α-branching for regio- and stereoselective reactions.

    View details for PubMedID 26630114

  • A catalytic asymmetric total synthesis of (-)-perophoramidine CHEMICAL SCIENCE Trost, B. M., Osipov, M., Krueger, S., Zhang, Y. 2015; 6 (1): 349-353

    View details for DOI 10.1039/c4sc01826e

    View details for Web of Science ID 000345901600039

  • A Catalytic Asymmetric Total Synthesis of (-)-Perophoramidine. Chemical science Trost, B. M., Osipov, M., Krüger, S., Zhang, Y. 2015; 6 (1): 349–53

    Abstract

    We report a catalytic asymmetric total synthesis of the ascidian natural product perophoramidine. The synthesis employs a molybdenum-catalyzed asymmetric allylic alkylation of an oxindole nucleophile and a monosubstituted allylic electrophile as a key asymmetric step. The enantioenriched oxindole product from this transformation contains vicinal quaternary and tertiary stereocenters, and is obtained in high yield along with high levels of regio-, diastereo-, and enantioselectivity. To install the second quaternary stereocenter in the target, the route utilizes a novel regio- and diastereoselective allylation of a cyclic imino ether to deliver an allylated imino ether product in near quantitative yield and with complete regio- and diastereocontrol. Oxidative cleavage and reductive amination are used as final steps to access the natural product.

    View details for PubMedID 25485074

    View details for PubMedCentralID PMC4251524

  • Construction of Enantioenriched [3.1.0] Bicycles via a Ruthenium-Catalyzed Asymmetric Redox Bicycloisomerization Reaction. Journal of the American Chemical Society Trost, B. M., Ryan, M. C., Rao, M., Markovic, T. Z. 2014; 136 (50): 17422-17425

    Abstract

    Enantiomerically enriched [3.1.0] bicycles containing vicinal quaternary centers were synthesized from [1,6]-enynes using a cyclopentadienylruthenium catalyst containing a tethered chiral sulfoxide. The reaction was complicated by the fact that the substrates contained a racemic propargyl alcohol that could affect the selectivity of the process. Nonetheless, high levels of enantioinduction were observed, despite complications arising from the use of racemic substrates. Mechanistic studies showed that while the utilization of either enantiomer of the propargyl alcohol led to high product enantiomeric ratios when the reaction was conducted in acetone, a significant matched/mismatched effect was observed in tetrahydrofuran.

    View details for DOI 10.1021/ja510968h

    View details for PubMedID 25420225

  • Asymmetric Stereodivergent Strategy Towards Aminocyclitols CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Malhotra, S. 2014; 20 (27): 8288-8292

    Abstract

    A concise asymmetric synthesis of aminocyclitols, such as diastereomeric 2-deoxystreptamine analogues and conduramine A, is described. The Pd-catalyzed asymmetric desymmetrization of meso 1,4-dibenzolate enables the synthesis of highly oxidized cyclohexane architectures. These scaffolds can potentially be used to access new aminoglycoside antibiotics and enantiomerically pure α-glucosidase inhibitors.

    View details for DOI 10.1002/chem.201402175

    View details for Web of Science ID 000338019300008

    View details for PubMedID 24889256

  • Palladium-Catalyzed Dearomative Trimethylenemethane Cycloaddition Reactions JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ehmke, V., O'Keefe, B. M., Bringley, D. A. 2014; 136 (23): 8213-8216

    Abstract

    A general protocol for the palladium-catalyzed dearomative trimethylenemethane [3+2] cycloaddition reaction with simple nitroarene substrates is described. This methodology leads to the exclusive formation of the dearomatized alicyclic products without subsequent rearomatization. The reaction is tolerant toward a broad range of heterocyclic and benzenoid substrates. The use of chiral bisdiamidophosphite ligands enabled the development of an enantioselective variant of this transformation, representing one of the rare examples of an asymmetric catalytic dearomatization process.

    View details for DOI 10.1021/ja5044825

    View details for Web of Science ID 000337336800018

    View details for PubMedID 24874093

  • An Approach for Rapid Increase in Molecular Complexity: Atom Economic Routes to Fused Polycyclic Ring Systems ORGANIC LETTERS Trost, B. M., Ehmke, V. 2014; 16 (10): 2708-2711

    Abstract

    A protocol for the asymmetric trimethylenemethane (TMM) [3 + 2] cycloaddition reaction of alkynyl-substituted TMM donors and unsaturated N-acyl pyrroles employing a chiral bisdiamidophosphite ligand has been developed. This process generates alkynyl-substituted cyclopentanes in high yields and diastereo- and enantioselectivities. These chiral precursors are employed for the atom economic assembly of fused polycyclic hydrocarbons with hydroindene, hydroazulene, and hydrocyclopentanaphthalene scaffolds by consecutive cycloaddition reactions.

    View details for DOI 10.1021/ol5009872

    View details for Web of Science ID 000336199200035

    View details for PubMedID 24787546

  • Structure and Reactivity of Late Transition Metal ?(3) -Benzyl Complexes. Angewandte Chemie (International ed. in English) Trost, B. M., Czabaniuk, L. C. 2014; 53 (11): 2826-2851

    Abstract

    The coordination of transition metals to organic fragments can yield complexes with fascinating and unexpected binding patterns. The study of metal-benzyl complexes has demonstrated the feasibility of η(3)-coordination, which results in a dearomatized ring. These complexes also offer insight into reaction mechanisms as proposed intermediates in catalytic cycles. In this Review we discuss the synthesis and characterization of these complexes with late transition metals and the subsequent development of catalytic benzylic functionalization methods, including asymmetric variants.

    View details for DOI 10.1002/anie.201305972

    View details for PubMedID 24554487

  • Development of ProPhenol Ligands for the Diastereo- and Enantioselective Synthesis of beta-Hydroxy-alpha-amino Esters JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Miege, F. 2014; 136 (8): 3016-3019

    View details for DOI 10.1021/ja4129394

    View details for Web of Science ID 000332144300022

  • A Concise Synthesis of (-)-Lasonolide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Stivala, C. E., Hull, K. L., Huang, A., Fandrick, D. R. 2014; 136 (1): 88-91

    Abstract

    Lasonolide A is a novel polyketide displaying potent anticancer activity across a broad range of cancer cell lines. Here, an enantioselective convergent total synthesis of the (-)-lasonolide A in 16 longest linear and 34 total steps is described. This approach significantly reduces the step count compared to other known syntheses. The synthetic strategy utilizes alkyne-bearing substrates as core building blocks and is highlighted by stitching together two similarly complex halves via a key Ru-catalyzed alkene-alkyne coupling and macrolactionization.

    View details for DOI 10.1021/ja411270d

    View details for Web of Science ID 000329586600023

    View details for PubMedID 24308383

  • Asymmetric synthesis of chiral cycloalkenone derivatives via palladium catalysis CHEMICAL SCIENCE Trost, B. M., Masters, J. T., Lumb, J., Fateen, D. 2014; 5 (4): 1354-1360

    View details for DOI 10.1039/c3sc53250j

    View details for Web of Science ID 000332467400011

  • Asymmetric synthesis of chiral cycloalkenone derivatives via palladium catalysis. Chemical science Trost, B. M., Masters, J. T., Lumb, J. P., Fateen, D. 2014; 5 (4): 1354–60

    Abstract

    The palladium-catalyzed oxidative desymmetrization of meso dibenzoates yields γ-benzoyloxy cycloalkenones in good yields and with excellent levels of enantioselectivity. These compounds serve as precursors to a broad range of substituted cycloalkenones, including well-established synthetic building blocks and elaborated cycloalkanone derivatives. The ability to prepare both enantiomers of the oxidative desymmetrization products enables a unified strategy toward stereochemically diverse epoxyquinoid natural products.

    View details for PubMedID 24761221

  • Development of ProPhenol ligands for the diastereo- and enantioselective synthesis of β-hydroxy-α-amino esters. Journal of the American Chemical Society Trost, B. M., Miege, F. 2014; 136 (8): 3016–19

    Abstract

    A zinc-ProPhenol-catalyzed direct asymmetric aldol reaction between glycine Schiff bases and aldehydes is reported. The design and synthesis of new ProPhenol ligands bearing 2,5-trans-disubstituted pyrrolidines was essential for the success of this process. The transformation operates at room temperature and affords syn β-hydroxy-α-amino esters in high yields with good to excellent levels of diastereo- and enantioselectivity.

    View details for PubMedID 24502188

    View details for PubMedCentralID PMC3985890

  • The toolbox of synthetic reactions: a key to unlock the design of structure for function. The Journal of organic chemistry Trost, B. M. 2014; 79 (21): 9913

    View details for PubMedID 25346192

  • A Chiral Sulfoxide-Ligated Ruthenium Complex for Asymmetric Catalysis: Enantio- and Regioselective Allylic Substitution JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rao, M., Dieskau, A. P. 2013; 135 (49): 18697-18704

    Abstract

    The design and synthesis of a novel chiral sulfoxide-ligated cyclopentadienyl ruthenium complex is described. Its utility as an asymmetric variant of [CpRu(MeCN)3]PF6 is demonstrated through its ability to function in the branched-selective asymmetric allylic alkylation of phenols and carboxylic acids. Water has also been shown to act as a competent nucleophile in this reaction to generate branched allyl alcohols with good regio- and enantioselectivities.

    View details for DOI 10.1021/ja411310w

    View details for Web of Science ID 000328438700067

    View details for PubMedID 24245989

  • Highly Substituted Enantioenriched Cyclopentane Derivatives by Palladium-Catalyzed [3+2] Trimethylenemethane Cycloadditions with Disubstituted Nitroalkenes ORGANIC LETTERS Trost, B. M., Bringley, D. A., O'Keefe, B. M. 2013; 15 (22): 5630-5633

    Abstract

    β,β-Disubstituted nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. The reaction provides access to heavily substituted cyclopentanes containing up to three contiguous stereocenters, and the products may be converted to both cyclopentylamines and cyclopentenones. A rare dependence of the sense of chirality of the cycloadducts was observed to be exclusively dependent on the structure of the palladium-bound trimethylenemethane intermediate.

    View details for DOI 10.1021/ol402487s

    View details for Web of Science ID 000327175500005

    View details for PubMedID 24161190

    View details for PubMedCentralID PMC3880620

  • Rapid Access to Spirocyclic Oxindole Alkaloids: Application of the Asymmetric Palladium-Catalyzed [3+2] Trimethylenemethane Cycloaddition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Bringley, D. A., Zhang, T., Cramer, N. 2013; 135 (44): 16720-16735

    Abstract

    The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.

    View details for DOI 10.1021/ja409013m

    View details for Web of Science ID 000326774300073

    View details for PubMedID 24083654

    View details for PubMedCentralID PMC3992010

  • Palladium-catalyzed asymmetric benzylation of azlactones. Chemistry (Weinheim an der Bergstrasse, Germany) Trost, B. M., Czabaniuk, L. C. 2013; 19 (45): 15210-15218

    Abstract

    Asymmetric benzylation of prochiral azlactone nucleophiles enables the catalytic introduction of a benzyl group towards the synthesis of α,α-disubstituted amino acids. Herein, we report an enantioselective palladium-catalyzed process using chiral bis(diphenylphosphinobenzoyl)diamine (dppba) ligands. Naphthalene- and heterocycle-based methyl carbonates react with a number of azlactones derived from both natural and unnatural amino acids. Monocyclic benzylic electrophiles, for which the barrier to ionization is higher, must employ a phosphate leaving group in order to react. Reaction conditions for electron-rich and -neutral benzylic electrophiles have been developed, and the scope of the reaction has been explored with respect to both reaction partners. The high levels of asymmetric induction, as well as the reactivity pattern of the electrophiles, suggest an η(3) -benzyl intermediate that arises through two distinct pathways.

    View details for DOI 10.1002/chem.201302390

    View details for PubMedID 24115047

  • Total Synthesis of (-)-18-epi-Peloruside A: An Alkyne Linchpin Strategy ORGANIC LETTERS Trost, B. M., Michaelis, D. J., Malhotra, S. 2013; 15 (20): 5274-5277

    View details for DOI 10.1021/oI4024997

    View details for Web of Science ID 000326121700033

  • Dinuclear zinc-ProPhenol-catalyzed enantioselective a-hydroxyacetate aldol reaction with activated ester equivalents. Organic letters Trost, B. M., Michaelis, D. J., Truica, M. I. 2013; 15 (17): 4516-4519

    Abstract

    An enantioselective α-hydroxyacetate aldol reaction that employs N-acetyl pyrroles as activated ester equivalents and generates syn 1,2-diols in good yield and diastereoselectivity is reported. This dinuclear zinc-ProPhenol-catalyzed transformation proceeds with high enantioselectivity with a wide variety of substrates including aryl, alyl, and alkenyl aldehydes. The resulting α,β-dihydroxy activated esters are versatile intermediates for the synthesis of a variety of carboxylic acid derivatives including amides, esters, and unsymmetrical ketones.

    View details for DOI 10.1021/ol402081p

    View details for PubMedID 23947595

    View details for PubMedCentralID PMC3812954

  • Palladium-catalyzed asymmetric construction of vicinal all-carbon quaternary stereocenters and its application to the synthesis of cyclotryptamine alkaloids. Angewandte Chemie (International ed. in English) Trost, B. M., Osipov, M. 2013; 52 (35): 9176-9181

    Abstract

    A twofold Pd-DAAA Pd-catalyzed decarboxylative allylic alkylation was used to construct two vicinal all-carbon quaternary stereocenters (marked in red) in a diastereo- and enantioselective fashion. The products of the Pd-DAAA were further elaborated to complete the formal syntheses of cyclotryptamine alkaloids. The twofold Pd-catalyzed transformation proceeds through an initial matched allylation followed by a second mismatched allylation to deliver the desired product.

    View details for DOI 10.1002/anie.201302805

    View details for PubMedID 23824625

  • Enantioselective construction of highly substituted vinylidenecylopentanes by palladium-catalyzed asymmetric [3+2] cycloaddition reaction. Angewandte Chemie (International ed. in English) Trost, B. M., Maruniak, A. 2013; 52 (24): 6262-6264

    Abstract

    A new cycloadduct: The title reaction of methylene-trimethylenemethane (TMM) with α,β-unsaturated N-acyl pyrroles is an efficient method for the construction of vinylidenecyclopentanes. An asymmetric protocol using this unique donor forms cycloadducts in excellent yield and enantioselectivity, making use of a bisdiamidophosphite ligand derived from trans-1,2-stilbenediamine.

    View details for DOI 10.1002/anie.201300275

    View details for PubMedID 23620437

  • Mechanism and Origins of Selectivity in Ru(II)-Catalyzed Intramolecular (5+2) Cycloadditions and Ene Reactions of Vinylcyclopropanes and Alkynes from Density Functional Theory JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hong, X., Trost, B. M., Houk, K. N. 2013; 135 (17): 6588-6600

    Abstract

    The mechanism, solvent effects, and origins of selectivities in Ru(II)-catalyzed intramolecular (5+2) cycloaddition and ene reaction of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory. B3LYP/6-31G(d)/LANL2DZ optimized structures were further evaluated with the M06 functional, 6-311+G(2d,p) and LANL2DZ basis sets, and the SMD solvent model. The favored mechanism involves an initial ene-yne oxidative cyclization to form a ruthenacyclopentene intermediate. This mechanism is different from that found earlier with rhodium catalysts. The subsequent β-hydride elimination and cyclopropane cleavage are competitive, determining the experimental selectivity. In trans-VCP, the cyclopropane cleavage is intrinsically favored and leads to the (5+2) cycloaddition product. Although the same intrinsic preferences occur with the cis-VCP, an unfavorable rotation is required in order to generate the cis-double bond in seven-membered ring product, which reverses the selectivity. Acetone solvent is found to facilitate the acetonitrile dissociation from the precatalyst, destabilizing the resting state of the catalyst and leading to a lower overall reaction barrier. In addition, the origins of diastereoselectivities when the allylic hydroxyl group is trans to the bridgehead hydrogen are found to be the electrostatic interactions. In the pathway that generates the favored diastereomer, the oxygen lone pairs from the substituent are closer to the cationic catalyst center and provide stabilizing electrostatic interactions. Similar pathways also determine the regioselectivities, that is, whether the more or less substituted C-C bond of cyclopropane is cleaved. In the trans-1,2-disubstitued cyclopropane substrate, the substituent from the cyclopropane is away from the reaction center in both pathways, and low regioselectivity is found. In contrast, the cleavage of the more substituted C-C bond of the cis-1,2-disubstituted cyclopropane has steric repulsions from the substituent, and thus higher regioselectivity is found.

    View details for DOI 10.1021/ja4012657

    View details for Web of Science ID 000318469100035

    View details for PubMedID 23611430

  • Regio- and Enantioselective Synthesis of Pyrrolidines Bearing a Quaternary Center by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethanes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lam, T. M., Herbage, M. A. 2013; 135 (7): 2459-2461

    Abstract

    Herein we describe the first use of disubstituted donors in the palladium-catalyzed trimethylenemethane (TMM) cycloaddition resulting in an enantioselective synthesis of highly substituted pyrrolidines. These cyanoalkyl donors 1 form all-carbon quaternary centers in a catalytic, asymmetric, and intermolecular manner uniquely using diamidophosphite ligands L2 and L3, generating synthetically important chiral building blocks in good yields and selectivities.

    View details for DOI 10.1021/ja312351s

    View details for Web of Science ID 000315373000016

    View details for PubMedID 23363050

  • Exploring the Unique Reactivity of Diazoesters: An Efficient Approach to Chiral beta-Amino Acids ORGANIC LETTERS Trost, B. M., Malhotra, S., Ellerbrock, P. 2013; 15 (3): 440-443

    Abstract

    The development of a highly stereospecific process for the C-O to C-N exchange with retention of configuration is described. This transformation enables access to optically enriched β-amido-α-diazoesters. These products are transformed to β-amino acids not readily accessible using known methods.

    View details for DOI 10.1021/ol303011f

    View details for Web of Science ID 000314559000004

    View details for PubMedID 23323996

  • Palladium-Catalyzed Enantioselective Allylic Alkylations through C-H Activation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Thaisrivongs, D. A., Donckele, E. J. 2013; 52 (5): 1523-1526

    View details for DOI 10.1002/anie.201207870

    View details for Web of Science ID 000313913300034

    View details for PubMedID 23233449

  • Total synthesis of (-)-18-epi-peloruside A: an alkyne linchpin strategy. Organic letters Trost, B. M., Michaelis, D. J., Malhotra, S. 2013; 15 (20): 5274–77

    Abstract

    A convergent synthetic route toward cytotoxic agent peloruside A that hinges on the use of an alkyne linchpin to assemble the natural product is described. Other highlights of this synthesis include an asymmetric desymmetrization reaction of a 1,3-diol, a one-pot conversion of a dibromoolefin to a stereodefined enone, and a diastereoselective aldol condensation. Misassignment of the absolute stereochemistry of the C18 stereocenter in our synthesis provided the natural product epimeric at the C18 ethyl stereocenter.

    View details for PubMedID 24490808

    View details for PubMedCentralID PMC3939827

  • Catalysis: Unlimited Frontiers - Our Early Personal Journey into the World of Palladium INVENTING REACTIONS Trost, B. M. 2013; 44: 1-12
  • Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Aryloxindoles with Allylidene Dipivalate: A Useful Enol Pivalate Product ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Masters, J. T., Burns, A. C. 2013; 52 (8): 2260-2264

    View details for DOI 10.1002/anie.201209783

    View details for Web of Science ID 000314998500024

    View details for PubMedID 23335176

  • Enantioselective Synthesis of 2,2-Disubstituted Tetrahydrofurans: Palladium-Catalyzed [3+2] Cycloadditions of Trimethylenemethane with Ketones ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Bringley, D. A. 2013; 52 (16): 4466-4469

    View details for DOI 10.1002/anie.201300616

    View details for Web of Science ID 000317615000030

    View details for PubMedID 23495134

  • Development of Zn-ProPhenol-Catalyzed Asymmetric Alkyne Addition: Synthesis of Chiral Propargylic Alcohols CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Bartlett, M. J., Weiss, A. H., Jacobi von Wangelin, A., Chan, V. S. 2012; 18 (51): 16498-16509

    Abstract

    The development of a general and practical zinc-catalyzed enantioselective alkyne addition methodology is reported. The commercially available ProPhenol ligand (1) has facilitated the addition of a wide range of zinc alkynylides to aryl, aliphatic, and α,β-unsaturated aldehydes in high yield and enantioselectivity. New insights into the mechanism of this reaction have resulted in a significant reduction in reagent stoichiometry, enabling the use of precious alkynes and avoiding the use of excess dimethylzinc. The enantioenriched propargylic alcohols from this reaction serve as versatile synthetic intermediates and have enabled efficient syntheses of several complex natural products.

    View details for DOI 10.1002/chem.201202085

    View details for Web of Science ID 000312275200029

    View details for PubMedID 23097281

    View details for PubMedCentralID PMC3864595

  • Total Synthesis of Aeruginosin 98B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Kaneko, T., Andersen, N. G., Tappertzhofen, C., Fahr, B. 2012; 134 (46): 18944-18947

    Abstract

    The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.

    View details for DOI 10.1021/ja309947n

    View details for Web of Science ID 000311324900017

    View details for PubMedID 23116136

    View details for PubMedCentralID PMC3551629

  • Diastereoselective Formation of Tetrahydrofurans via Pd-Catalyzed Asymmetric Allylic Alkylation: Synthesis of the C13-C29 Subunit of Amphidinolide N ORGANIC LETTERS Trost, B. M., Rey, J. 2012; 14 (22): 5632-5635

    Abstract

    An efficient synthesis of the C13-C29 fragment of amphidinolide N is described. The synthesis relies on a new strategy involving Pd-catalyzed asymmetric allylic alkylation to generate diastereoselectively the cis- or trans-THF unit simply by varying the enantiomer of the ligand. The C19 hydroxyl-bearing stereocenter was introduced using a chelation-controlled allylation which led exclusively to a single diastereoisomer.

    View details for DOI 10.1021/ol302409g

    View details for Web of Science ID 000311324100004

    View details for PubMedID 23098131

    View details for PubMedCentralID PMC3501412

  • Palladium-Catalyzed Diastereo- and Enantioselective Formal [3+2]-Cycloadditions of Substituted Vinylcyclopropanes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Morris, P. J., Sprague, S. J. 2012; 134 (42): 17823-17831

    Abstract

    We describe a palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloaddition between substituted vinylcyclopropanes and electron-deficient olefins in the form of azlactone- and Meldrum's acid alkylidenes to give highly substituted cyclopentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle.

    View details for DOI 10.1021/ja309003x

    View details for Web of Science ID 000310103800081

    View details for PubMedID 23030714

    View details for PubMedCentralID PMC3495600

  • Asymmetric Catalytic Synthesis of the Proposed Structure of Trocheliophorolide B ORGANIC LETTERS Trost, B. M., Quintard, A. 2012; 14 (17): 4698-4700

    Abstract

    A concise catalytic asymmetric synthesis of the proposed structure of trocheliophorolide B is reported. The synthetic sequence notably features an asymmetric acetaldehyde alkynylation, a Ru-catalyzed alder-ene reaction, and a Zn-ProPhenol ynone aldol condensation. Comparison with the reported data suggests a misassignment of the natural product structure.

    View details for DOI 10.1021/ol302074h

    View details for Web of Science ID 000308390000103

    View details for PubMedID 22913543

    View details for PubMedCentralID PMC3439167

  • Enantioselective synthesis of tertiary a-hydroxyketones from unfunctionalized ketones: palladium-catalyzed asymmetric allylic alkylation of enolates. Angewandte Chemie (International ed. in English) Trost, B. M., Koller, R., Schäffner, B. 2012; 51 (33): 8290-8293

    View details for DOI 10.1002/anie.201203663

    View details for PubMedID 22829317

  • Synthesis of alpha-allylated alpha,beta-unsaturated carbonyl compounds using vanadium/palladium contemporaneous dual catalysis NATURE PROTOCOLS Trost, B. M., Luan, X. 2012; 7 (8): 1497-1501
  • Development of Diamidophosphite Ligands and Their Application to the Palladlium-Catalyzed Vinyl-Substituted Trimethylenemethane Asymmetric [3+2] Cycloaddition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lam, T. M. 2012; 134 (28): 11319-11321

    Abstract

    A palladium-catalyzed asymmetric [3 + 2] cycloaddition of a vinyl-substituted trimethylenemethane (TMM) donor with α,β-unsaturated acyl imidazoles is described. A newly designed bisdiamidophosphite ligand derived from (S,S)-trans-1,2-cyclohexanediamine and (2R,4R)-pentanediol has been instrumental for the development of this process. This transformation generates tetrasubstituted cyclopentanes bearing three contiguous stereocenters in high yields, with good diastereo- and enantioselectivity.

    View details for DOI 10.1021/ja305717r

    View details for Web of Science ID 000306457900006

    View details for PubMedID 22716661

  • Dinuclear Zinc Catalyzed Asymmetric Spirannulation Reaction: An Umpolung Strategy for Formation of alpha-Alkylated-alpha-Hydroxyoxindoles ORGANIC LETTERS Trost, B. M., Hirano, K. 2012; 14 (10): 2446-2449

    View details for DOI 10.1021/ol300577y

    View details for Web of Science ID 000304129000005

  • Palladium-Catalyzed Asymmetric Allylic Alkylation of Electron-Deficient Pyrroles with Meso Electrophiles ORGANIC LETTERS Trost, B. M., Osipov, M., Dong, G. 2012; 14 (9): 2254-2257

    Abstract

    Pyrroles can serve as competent nucleophiles with meso electrophiles in the Pd-catalyzed asymmetric allylic alkylation. The products from this transformation were obtained as a single regio- and diastereomer in high yield and enantiopurity. A nitropyrrole-containing nucleoside analogue was synthesized in seven steps to demonstrate the synthetic utility of this transformation.

    View details for DOI 10.1021/ol3006584

    View details for Web of Science ID 000303492200016

    View details for PubMedID 22506671

    View details for PubMedCentralID PMC3407807

  • Atom-Economical Synthesis of Functionalized Cycloalkanes via Catalytic Redox Cycloisomerization of Propargyl Alcohols ORGANIC LETTERS Trost, B. M., Breder, A., Kai, B. 2012; 14 (7): 1708-1711

    Abstract

    An atom-economical procedure for the direct synthesis of cycloalkanes from propargyl alcohols is reported. This high-yielding one-pot process involves a sequence consisting of a Ru-catalyzed redox isomerization of ynols into enones or an enal followed by an intramolecular Michael addition of a variety of carbon nucleophiles. Furthermore, an asymmetric variant of this protocol realized by the aid of a chiral nonracemic diamine catalyst, which provides the cyclization products in up to 97% ee, is presented.

    View details for DOI 10.1021/ol300278x

    View details for PubMedID 22416797

  • Benzylic Phosphates as Electrophiles in the Palladium-Catalyzed Asymmetric Benzylation of Azlactones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Czabaniuk, L. C. 2012; 134 (13): 5778-5781

    Abstract

    Palladium-catalyzed asymmetric benzylation has been demonstrated with azlactones as prochiral nucleophiles in the presence of chiral bisphosphine ligands. Benzylic electrophiles are utilized under two sets of reaction conditions to construct a new tetrasubstituted stereocenter. Electron density of the phenyl ring dictates the reaction conditions, including the leaving group. The reported methodology represents a novel asymmetric carbon-carbon bond formation in an amino acid precursor.

    View details for DOI 10.1021/ja301461p

    View details for Web of Science ID 000302490000016

    View details for PubMedID 22420708

  • Enantioselective Construction of Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Silverman, S. M. 2012; 134 (10): 4941-4954

    Abstract

    A protocol for the enantioselective [3 + 2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complementary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters.

    View details for DOI 10.1021/ja210981a

    View details for Web of Science ID 000301990600071

    View details for PubMedID 22309214

    View details for PubMedCentralID PMC3407810

  • Transition-Metal-Catalyzed Synthesis of Aspergillide B: An Alkyne Addition Strategy ORGANIC LETTERS Trost, B. M., Bartlett, M. J. 2012; 14 (5): 1322-1325

    Abstract

    A catalytic enantioselective formal total synthesis of aspergillide B is reported. This linchpin synthesis was enabled by the development of new conditions for Zn-ProPhenol catalyzed asymmetric alkyne addition. This reaction was used in conjunction with ruthenium-catalyzed trans-hydrosilylation to affect the rapid construction of a late-stage synthetic intermediate of aspergillide B to complete a formal synthesis of aspergillide B in a highly efficient manner.

    View details for DOI 10.1021/ol300200m

    View details for Web of Science ID 000300916000035

    View details for PubMedID 22356535

    View details for PubMedCentralID PMC3407809

  • Total Synthesis of Laulimalide: Assembly of the Fragments and Completion of the Synthesis of the Natural Product and a Potent Analogue CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Amans, D., Seganish, W. M., Chung, C. K. 2012; 18 (10): 2961-2971

    Abstract

    Herein, we present a full account of our efforts to couple the northern and the southern building blocks, the synthesis of which were described in the preceding paper, along with the modifications required to ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle, followed by a highly stereoselective 1,3-allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report a second generation route that provides a more concise synthesis of the natural product.

    View details for DOI 10.1002/chem.201102899

    View details for Web of Science ID 000300837100027

    View details for PubMedID 22307856

    View details for PubMedCentralID PMC3517067

  • Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Seganish, W. M., Chung, C. K., Amans, D. 2012; 18 (10): 2948-2960

    Abstract

    The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru-catalyzed alkene-alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh-catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six-membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.

    View details for DOI 10.1002/chem.201102898

    View details for Web of Science ID 000300837100026

    View details for PubMedID 22307837

    View details for PubMedCentralID PMC3517066

  • Pd- and Mo-Catalyzed Asymmetric Allylic Alkylation ORGANIC PROCESS RESEARCH & DEVELOPMENT Trost, B. M. 2012; 16 (2): 185-194

    View details for DOI 10.1021/op200294r

    View details for Web of Science ID 000300339700003

  • Development of the Enantioselective Addition of Ethyl Diazoacetate to Aldehydes: Asymmetric Synthesis of 1,2-Diols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Malhotra, S., Koschker, P., Ellerbrock, P. 2012; 134 (4): 2075-2084

    Abstract

    A novel synthetic strategy toward the asymmetric synthesis of vicinal diols bearing a tertiary center is presented. The method encompasses the dinuclear Mg-catalyzed asymmetric addition of ethyl diazoacetate into several aldehydes, oxidation of the diazo functionality, and diastereoselective alkyl transfer of various organometallics into the resulting chiral β-hydroxy-α-ketoesters to afford a diverse range of 1,2-diols in high yield, diastereoselectivity, and chirality transfer.

    View details for DOI 10.1021/ja206995s

    View details for Web of Science ID 000301084600043

    View details for PubMedID 22088096

    View details for PubMedCentralID PMC3271135

  • Thionium Ion Initiated Medium-Sized Ring Formation: The Total Synthesis of Asteriscunolide D JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Burns, A. C., Bartlett, M. J., Tautz, T., Weiss, A. H. 2012; 134 (3): 1474-1477

    Abstract

    The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.

    View details for DOI 10.1021/ja210986f

    View details for Web of Science ID 000301084400024

    View details for PubMedID 22236456

    View details for PubMedCentralID PMC3268366

  • Enantioselective Palladium-Catalyzed [3+2] Cycloadditions of Trimethylenemethane with Nitroalkenes ORGANIC LETTERS Trost, B. M., Bringley, D. A., Seng, P. S. 2012; 14 (1): 234-237

    Abstract

    Nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. Furthermore, the products thus formed are highly versatile synthetic intermediates and provide convenient access to both cyclopentylamines and cyclopentenones.

    View details for DOI 10.1021/ol2030179

    View details for Web of Science ID 000298828500060

    View details for PubMedID 22176260

    View details for PubMedCentralID PMC3268375

  • Tandem Palladium(0) and Palladium(II)-Catalyzed Allylic Alkylation Through Complementary Redox Cycles ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Thaisrivongs, D. A., Hansmann, M. M. 2012; 51 (46): 11522-11526

    View details for DOI 10.1002/anie.201204251

    View details for Web of Science ID 000310875700019

    View details for PubMedID 23055351

  • Pd and Mo Catalyzed Asymmetric Allylic Alkylation. Organic process research & development Trost, B. M. 2012; 16 (2): 185–94

    Abstract

    The ability to control the alkylation of organic substrates becomes ever more powerful by using metal catalysts. Among the major benefits of metal catalysis is the possibility to perform such processes asymmetrically using only catalytic amounts of the chiral inducing agent which is a ligand to the metal of the catalyst. A unique aspect of asymmetric metal catalyzed processes is the fact that many mechanisms exist for stereoinduction. Furthermore, using the same catalyst system, many types of bonds including but not limited to C-C, C-N, C-O, C-S, C-P, and C-H can be formed asymmetrically. An overview of this process using palladium and molybdenum based metals being developed in my laboratories and how they influence strategy in synthesizing bioactive molecular targets is presented.

    View details for PubMedID 22736934

    View details for PubMedCentralID PMC3377172

  • Synthesis of α-allylated α,β-unsaturated carbonyl compounds using vanadium/palladium contemporaneous dual catalysis. Nature protocols Trost, B. M., Luan, X. 2012; 7 (8): 1497–1501

    Abstract

    This protocol describes a new approach for the preparation of α-allylated α,β-unsaturated carbonyl compound by chemoselective cross-coupling of propargyl alcohols with allyl carbonates using an unprecedented vanadium/palladium contemporaneous dual catalysis. This process involves 1,3-transposition of propargyl alcohols by an oxyvanadium catalyst to generate vanadium allenoates and the activation of allyl carbonates by a palladium catalyst to generate π-allylpalladium species. These two active intermediates trap each other more rapidly to afford the observed product, rather than being intercepted by the large excess of starting propargyl alcohol. One example for the preparation of this type of α-allylated α,β-unsaturated carbonyl compound is included in the text. It takes ~20 h to complete the protocol: 1.0 h to set up the reaction, 16 h for the reaction and 2.0 h for isolation and purification. This chemistry has been applied to obtain a wide range of α-allylated α,β-unsaturated ketones, esters and amides, which are highly valuable building blocks in organic synthesis.

    View details for PubMedID 22790085

  • Palladium-Catalyzed Alkylation of 1,4-Dienes by C?H Activation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Hansmann, M. M., Thaisrivongs, D. A. 2012; 51 (20): 4950-4953

    Abstract

    Activated: the title reaction proceeds with a broad range of nucleophiles and variously substituted 1,4-dienes under mild conditions, and provides direct access to the corresponding 1,3-diene-containing products with high regio- and stereocontrol (see scheme; 2,6-DMBQ=2,6-dimethylbenzoquinone, EWG=electron-withdrawing group). This is the first catalytic allylic C-H alkylation that proceeds in the absence of sulfoxide ligands.

    View details for DOI 10.1002/anie.201200601

    View details for Web of Science ID 000303925200034

    View details for PubMedID 22489024

  • Dinuclear zinc catalyzed asymmetric spirannulation reaction: an umpolung strategy for formation of α-alkylated-α-hydroxyoxindoles. Organic letters Trost, B. M., Hirano, K. 2012; 14 (10): 2446–49

    Abstract

    A highly diastereo- and enantioselective formal [3 + 2] cycloaddition of α,β-unsaturated esters and 3-hydroxyoxindoles catalyzed by a dinuclear zinc-ProPhenol complex is reported. The stereoselective Michael additions of 3-hydroxyoxindoles and the subsequent transesterifications afford spirocyclic δ-lactones.

    View details for PubMedID 22545918

  • Asymmetric Catalytic Alkynylation of Acetaldehyde: Application to the Synthesis of (+)-Tetrahydropyrenophorol ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Quintard, A. 2012; 51 (27): 6704-6708

    View details for DOI 10.1002/anie.201203035

    View details for Web of Science ID 000305987900030

    View details for PubMedID 22674869

  • Palladium-Catalyzed Allylic Alkylation of Carboxylic Acid Derivatives: N-Acyloxazolinones as Ester Enolate Equivalents ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Michaelis, D. J., Charpentier, J., Xu, J. 2012; 51 (1): 204-208

    View details for DOI 10.1002/anie.201105801

    View details for Web of Science ID 000298598500033

    View details for PubMedID 22095749

    View details for PubMedCentralID PMC3517038

  • Enantioselective Allylic Substitutions in Natural Product Synthesis TRANSITION METAL CATALYZED ENANTIOSELECTIVE ALLYLIC SUBSTITUTION IN ORGANIC SYNTHESIS Trost, B. M., Crawley, M. L. 2012; 38: 321-340
  • Enantioselective Synthesis of Tertiary a-Hydroxyketones from Unfunctionalized Ketones: Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Koller, R., Schaeffner, B. 2012; 51 (33): 8290-8293
  • Highly Stereoselective Synthesis of a-Alkyl-a-Hydroxycarboxylic Acid Derivatives Catalyzed by a Dinuclear Zinc Complex ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Hirano, K. 2012; 51 (26): 6480-6483

    Abstract

    A dinuclear zinc-ProPhenol catalyst enables highly enantioselective nitro-Michael reactions with oxazol-4(5H)-ones as nucleophilic substrates (see scheme, Nap = 2-naphthyl). This work highlights the utility of the ProPhenol family of ligands. The modular nature of these ligands proved crucial in the optimization of reaction conditions to achieve excellent stereoselectivities.

    View details for DOI 10.1002/anie.201201116

    View details for Web of Science ID 000305554500037

    View details for PubMedID 22644705

  • The Palladium Catalyzed Asymmetric Addition of Oxindoles and Allenes: An Atom-Economical Versatile Method for the Construction of Chiral Indole Alkaloids JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xie, J., Sieber, J. D. 2011; 133 (50): 20611-20622

    Abstract

    The Pd-catalyzed asymmetric allylic alkylation (AAA) is one of the most useful and versatile methods for asymmetric synthesis known in organometallic chemistry. Development of this reaction over the past 30 years has typically relied on the use of an allylic electrophile bearing an appropriate leaving group to access the reactive Pd(π-allyl) intermediate that goes on to the desired coupling product after attack by the nucleophile present in the reaction. Our group has been interested in developing alternative approaches to access the reactive Pd(π-allyl) intermediate that does not require the use of an activated electrophile, which ultimately generates a stoichiometric byproduct in the reaction that is derived from the leftover leaving group. Along these lines, we have demonstrated that allenes can be used to generate the reactive Pd(π-allyl) intermediate in the presence of an acid cocatalyst, and this system is compatible with nucleophiles to allow for formation of formal AAA products by Pd-catalyzed additions to allenes. This article describes our work regarding the use of oxindoles as carbon-based nucleophiles in a Pd-catalyzed asymmetric addition of oxindoles to allenes (Pd-catalyzed hydrocarbonation of allenes). By using the chiral standard Trost ligand (L1) and 3-aryloxindoles as nucleophiles, this hydrocarbonation reaction provides products with two vicinal stereocenters, with one being quaternary, in excellent chemo-, regio-, diastereo-, and enantioselectivities in high chemical yields.

    View details for DOI 10.1021/ja209244m

    View details for Web of Science ID 000298713600084

    View details for PubMedID 22070545

    View details for PubMedCentralID PMC3241881

  • Development of an Asymmetric Trimethylenemethane Cycloaddition Reaction: Application in the Enantioselective Synthesis of Highly Substituted Carbocycles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Silverman, S. M., Stambuli, J. P. 2011; 133 (48): 19483-19497

    Abstract

    A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with electron-deficient olefins has been developed. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic pyrrolidine and azetidine structures, is discussed. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired methylenecyclopentanes with high levels of enantioselectivity. The donor scope was also explored, and substituted systems were tolerated, including one bearing a nitrile moiety. These donors were reactive with unsaturated acylpyrroles, giving the product cyclopentane rings bearing three stereocenters in high enantioselectivity and complete diastereoselectivity.

    View details for DOI 10.1021/ja207550t

    View details for Web of Science ID 000297606500041

    View details for PubMedID 21936576

    View details for PubMedCentralID PMC3235052

  • Readily Accessible Chiral Diene Ligands for Rh-Catalyzed Enantioselective Conjugate Additions of Boronic Acids ORGANIC LETTERS Trost, B. M., Burns, A. C., Tautz, T. 2011; 13 (17): 4566-4569

    Abstract

    Enabled by the broad scope of the Pd-catalyzed asymmetric alkylation of meso- and d,l-divinylethylene carbonate, several chiral diene ligands were prepared in two steps from commercial materials. Subsequently, these ligands were evaluated in the Rh-catalyzed asymmetric conjugate addition of boronic acids to enones.

    View details for DOI 10.1021/ol201754c

    View details for Web of Science ID 000294242600023

    View details for PubMedID 21834567

  • Palladium-Catalyzed Asymmetric Allylic Alkylations of Polynitrogen-Containing Aromatic Heterocycles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Thaisrivongs, D. A., Hartwig, J. 2011; 133 (32): 12439-12441

    Abstract

    We report the palladium-catalyzed asymmetric allylic alkylation (AAA) reaction of a variety of nitrogen-containing aromatic heterocycles, including pyrazine, pyrimidine, pyridazine, quinoxaline, and benzoimidazole derivatives. The mesityl ester, whose steric bulk prevents competitive deacylation of the electrophile from "hard" nucleophiles, is introduced as a new leaving group in allylic alkylation chemistry. In contrast to our previous studies of AAA reactions with pyridine-based substrates, no precomplexation with a Lewis acid is required before deprotonation with LiHMDS, underscoring the relative acidity of these electron-deficient nucleophiles.

    View details for DOI 10.1021/ja205523e

    View details for Web of Science ID 000294740000032

    View details for PubMedID 21770467

  • Contemporaneous Dual Catalysis: Chemoselective Cross-Coupling of Catalytic Vanadium-Allenoate and pi-Allyipalladium Intermediates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Luan, X., Miller, Y. 2011; 133 (32): 12824-12833

    Abstract

    This paper presents a detailed investigation of a dual catalytic system that combines a vanadium-catalyzed Meyer-Schuster rearrangement and a palladium-catalyzed allylic alkylation. The implementation of this novel reaction relies on matching the formation rates of vanadium-allenoate and π-allylpalladium intermediates with their bimolecular coupling rate in order to minimize the undesired protonation or O-alkylation of the catalytically generated intermediates. Chemoselectivity in this dual catalytic process was successfully achieved by adjusting ligand structure and catalyst loading ratios of the vanadium and palladium catalysts. A great range of coupling partners for both the propargyl alcohol and allyl carbonate components are readily accommodated in this new transformation, which in turn provides a novel avenue to a variety of α-allylated α,β-unsaturated ketones, esters, and amides in moderate to excellent isolated yields.

    View details for DOI 10.1021/ja204817y

    View details for Web of Science ID 000294740000079

    View details for PubMedID 21714524

  • Total Syntheses of Bryostatins: Synthesis of Two Ring-Expanded Bryostatin Analogues and the Development of a New-Generation Strategy to Access the C7-C27 Fragment CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Yang, H., Dong, G. 2011; 17 (35): 9789-9805

    Abstract

    Herein, we report the synthesis of novel ring-expanded bryostatin analogues. By carefully modifying the substrate, a selective and high-yielding Ru-catalyzed tandem enyne coupling/Michael addition was employed to construct the northern fragment. Ring-closing metathesis was utilized to form the 31-membered ring macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty in forming the C16-C17 olefin at a late stage, we also describe our development of a new-generation strategy to access the C7-C27 fragment, containing both the ring B and C subunits.

    View details for DOI 10.1002/chem.201002932

    View details for Web of Science ID 000295001100030

    View details for PubMedID 21780195

    View details for PubMedCentralID PMC3517064

  • Atom-Economic and Stereoselective Syntheses of the Ring A and B Subunits of the Bryostatins CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Yang, H., Brindle, C. S., Dong, G. 2011; 17 (35): 9777-9788

    Abstract

    This article describes chemoselective and atom-economic methods for the stereoselective assembly of the ring A and B subunits of bryostatins. A Ru-catalyzed tandem alkene-alkyne coupling/Michael addition reaction was developed and applied to the synthesis of bryostatin ring B. We explored an acetylide-mediated epoxide-opening/6-exo-dig cyclization route to access the bryostatin ring A, although ring A was eventually furnished through an acid-catalyzed tandem transketalization/ketalization sequence. In addition, a dinuclear zinc-catalyzed methyl vinyl ketone (MVK) aldol strategy was evaluated for the construction of the polyacetate moiety. Utilization of these methods ultimately led to the rapid assembly of the northern bryostatin fragment containing both the ring A and B subunits.

    View details for DOI 10.1002/chem.201002930

    View details for Web of Science ID 000295001100029

    View details for PubMedID 21774000

    View details for PubMedCentralID PMC3517072

  • Total Synthesis of Bryostatins: The Development of Methodology for the Atom-Economic and Stereoselective Synthesis of the Ring C Subunit CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Frontier, A. J., Thiel, O. R., Yang, H., Dong, G. 2011; 17 (35): 9762-9776

    Abstract

    Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins.

    View details for DOI 10.1002/chem.201002898

    View details for Web of Science ID 000295001100028

    View details for PubMedID 21793057

    View details for PubMedCentralID PMC3437499

  • Synthesis and Reactivity of Unique Heterocyclic Structures en Route to Substituted Diamines ORGANIC LETTERS Olson, D. E., Maruniak, A., Malhotra, S., Trost, B. M., Du Bois, J. 2011; 13 (13): 3336-3339

    Abstract

    Rhodium-catalyzed oxidative cyclization of allylic hydroxylamine-derived sulfamate esters furnishes a novel family of bicyclic aziridines that serve as functional precursors to substituted diamines. Investigations with the N4-Troc form of these heterocycles have led to manifold improvements in reaction performance and scope and have revealed unique differences in the stability and reactivity of such compounds dictated by the choice of N4-protecting group.

    View details for DOI 10.1021/ol2010769

    View details for Web of Science ID 000291920800013

    View details for PubMedID 21618989

    View details for PubMedCentralID PMC3123413

  • Development of a Flexible Strategy towards FR900482 and the Mitomycins CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., O'Boyle, B. M., Torres, W., Ameriks, M. K. 2011; 17 (28): 7890-7903

    Abstract

    FR900482 and the mitomycins are two intriguing classes of alkaloid natural products that have analogous biological mechanisms and obvious structural similarity. Both classes possess potent anticancer activity, a feature that has led to their investigation and implementation for the clinical treatment of human cancer. Given the structural similarity between these natural products, we envisioned a common synthetic strategy by which both classes could be targeted through assembling the mitomycin skeleton prior to further oxidative functionalization. Realization of this strategy with respect to FR900482 was accomplished through the synthesis of 7-epi-FR900482, which displayed equal potency relative to the natural product against two human cancer cell lines. With the challenging goal of a synthesis of either mitomycin or FR900482 in mind, several methodologies were explored. While not all of these methods ultimately proved useful for our synthetic goal, a number of them led to intriguing findings that provide a more complete understanding of several methodologies. In particular, amination via π-allyl palladium complexes for the synthesis of tetrahydroquinolines, eight-membered heterocycle formation via carbonylative lactamization, and amination through late-stage C-H insertion via rhodium catalysis all featured prominently in our synthetic studies.

    View details for DOI 10.1002/chem.201003489

    View details for Web of Science ID 000293383300027

    View details for PubMedID 21618622

    View details for PubMedCentralID PMC3706290

  • Acetoxy Meldrum's Acid: A Versatile Acyl Anion Equivalent in the Pd-Catalyzed Asymmetric Allylic Alkylation ORGANIC LETTERS Trost, B. M., Osipov, M., Kaib, P. S., Sorum, M. T. 2011; 13 (12): 3222-3225

    Abstract

    Acetoxy Meldrum's acid can serve as a versatile acyl anion equivalent in the Pd-catalyzed asymmetric allylic alkylation. The reaction of this nucleophile with various meso and racemic electrophiles afforded alkylated products in high yields and enantiopurities. These enantioenriched products are versatile intermediates that can be further functionalized using nitrogen- and oxygen-centered nucleophiles, affording versatile scaffolds for the synthesis of nucleoside analogues. These scaffolds were used to complete formal syntheses of the anti-HIV drugs carbovir, abacavir, and the antibiotic aristeromycin.

    View details for DOI 10.1021/ol2011242

    View details for Web of Science ID 000291409800063

    View details for PubMedID 21615099

    View details for PubMedCentralID PMC3144701

  • A New Strategy for the Synthesis of Chiral beta-Alkynyl Esters via Sequential Palladium and Copper Catalysis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Taft, B. R., Masters, J. T., Lumb, J. 2011; 133 (22): 8502-8505

    Abstract

    A new strategy for the synthesis of chiral β-alkynyl esters which relies on sequential Pd and Cu catalysis is reported. Terminal alkynes bearing aryl, alkyl, and silyl groups can be employed without prior activation yielding a wide range of important chiral building blocks. The reaction sequence utilizes a robust Pd(II)-catalyzed hydroalkynylation of ynoates with terminal alkynes providing geometrically pure ynenoates which are readily reduced by CuH. In contrast to previous reports, where additions to ynenoates proceed with marginal preference for the 1,6-pathway, this conjugate reduction occurs with high 1,4-selectivity yielding β-alkynyl esters with excellent levels of enantioselectivity. Importantly, the method tolerates a wide range of functionality, including allylic carbonates and carbamates, and thus allows for rapid elaboration of the β-alkynyl esters into a variety of chiral, substituted heterocycles.

    View details for DOI 10.1021/ja203171x

    View details for Web of Science ID 000291414400031

    View details for PubMedID 21557627

    View details for PubMedCentralID PMC3235047

  • A Highly Enantio- and Diastereoselective Molybdenum-Catalyzed Asymmetric Allylic Alkylation of Cyanoesters JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Miller, J. R., Hoffman, C. M. 2011; 133 (21): 8165-8167

    Abstract

    An efficient molybdenum-catalyzed asymmetric allylic alkylation (Mo-AAA) of cyanoester nucleophiles is reported. A number of highly functionalized branched cyanoesters containing a quaternary carbon stereocenter with a vicinal tertiary stereocenter are obtained. This method generates a number of functionalized cyanoesters in excellent yield and chemoselectivity in good to excellent diastereoselectivity and enantioselectivity.

    View details for DOI 10.1021/ja2029602

    View details for Web of Science ID 000291459100028

    View details for PubMedID 21534526

  • Asymmetric Synthesis of Methylenetetrahydrofurans by Palladium-Catalyzed [3+2] Cycloaddition of Trimethylenemethane with Aldehydes - A Novel Ligand Design JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Bringley, D. A., Silverman, S. M. 2011; 133 (20): 7664-7667

    Abstract

    The palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with aldehydes is a direct and efficient route to methylenetetrahydrofurans. Herein we describe the first asymmetric synthesis of methylenetetrahydrofurans utilizing a palladium-TMM complex in the presence of a novel phosphoramidite ligand possessing a stereogenic phosphorus. The method allows for the formation of chiral disubstituted tetrahydrofurans in good yields and enantioselectivities.

    View details for DOI 10.1021/ja201181g

    View details for Web of Science ID 000291580400012

    View details for PubMedID 21513358

    View details for PubMedCentralID PMC3097301

  • Exercising Regiocontrol in Palladium-Catalyzed Asymmetric Prenylations and Geranylation: Unifying Strategy toward Flustramines A and B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Malhotra, S., Chan, W. H. 2011; 133 (19): 7328-7331

    Abstract

    Pd-catalyzed asymmetric prenylation of oxindoles to afford selectively either the prenyl or reverse-prenyl product has been demonstrated. Control of the regioselectivity in this transformation is governed by the choice of ligand, solvent, and halide additive. The resulting prenylated and reverse-prenylated products were transformed into ent-flustramides and ent-flustramines A and B. Additionally, control of the regio- and diastereoselectivity was obtained using π-geranylpalladium complexes.

    View details for DOI 10.1021/ja2020873

    View details for Web of Science ID 000290782200024

    View details for PubMedID 21520958

    View details for PubMedCentralID PMC3144703

  • Ligand-accelerated Enantioselective Propargylation of Aldehydes via Allenylzinc Reagents ORGANIC LETTERS Trost, B. M., Ngai, M., Dong, G. 2011; 13 (8): 1900-1903

    Abstract

    An enantioselective propargylation of aldehydes using an allenylzinc reagent generated in situ via a zinc-iodine exchange reaction is described. The enantioselectivity is controlled by addition of a catalytic amount of readily accessible and highly tunable amino alcohol ligand L13. A wide range of aldehydes can be propargylated to afford valuable and versatile homopropargyl alcohols in good to excellent yields with high levels of enantiopurity.

    View details for DOI 10.1021/ol200043n

    View details for Web of Science ID 000289187200002

    View details for PubMedID 21391717

  • Propargyl Alcohols as beta-Oxocarbenoid Precursors for the Ruthenium-Catalyzed Cyclopropanation of Unactivated Olefins by Redox Isomerization JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Breder, A., O'Keefe, B. M., Rao, M., Franz, A. W. 2011; 133 (13): 4766-4769

    Abstract

    An atom-economical method for the direct synthesis of [3.1.0]- and [4.1.0]-bicyclic frameworks via Ru-catalyzed redox bicycloisomerization of enynols is reported. The presented results highlight the unique reactivity profile of propargyl alcohols, which function as β-oxocarbene precursors, in the presence of a ruthenium(II) complex. Furthermore, a rare case of a formal vinylic C-H insertion reaction is described.

    View details for DOI 10.1021/ja200971v

    View details for Web of Science ID 000289492700028

    View details for PubMedID 21401098

  • Palladium-catalyzed decarboxylative asymmetric allylic alkylation of ß-ketoesters: an unusual counterion effect. Angewandte Chemie (International ed. in English) Trost, B. M., Schäffner, B., Osipov, M., Wilton, D. A. 2011; 50 (15): 3548-3551

    View details for DOI 10.1002/anie.201007803

    View details for PubMedID 21452369

  • Development of a Concise Synthesis of (-)-Oseltamivir (Tamiflu) CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Zhang, T. 2011; 17 (13): 3630-3643

    Abstract

    We report a full account of our work towards the development of an eight-step synthesis of anti-influenza drug (-)-oseltamivir (Tamiflu) from commercially available starting materials. The final synthetic route proceeds with an overall yield of 30 %. Key transformations include a novel palladium-catalyzed asymmetric allylic alkylation reaction (Pd-AAA) as well as a rhodium-catalyzed chemo-, regio-, and stereoselective aziridination reaction.

    View details for DOI 10.1002/chem.201003454

    View details for Web of Science ID 000288565800015

    View details for PubMedID 21365707

    View details for PubMedCentralID PMC3079541

  • Molybdenum-Catalyzed Asymmetric Allylic Alkylation of 3-Alkyloxindoles: Reaction Development and Applications CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Zhang, Y. 2011; 17 (10): 2916-2922

    Abstract

    We report a full account of our work towards the development of Mo-catalyzed asymmetric allylic alkylation reactions with 3-alkyloxindoles as nucleophiles. The reaction is complementary to the Pd-catalyzed reaction with regard to the scope of oxindole nucleophiles. A number of 3-alkyloxindoles were alkylated successfully under mild conditions to give products with excellent yields and good-to-excellent enantioselectivities. Applications of this method to the preparation of indoline alkaloids such as (-)-physostigmine, ent-(-)-debromoflustramine B, and the indolinoquinoline rings of communesin B are reported.

    View details for DOI 10.1002/chem.201002569

    View details for Web of Science ID 000288098200016

    View details for PubMedID 21290436

    View details for PubMedCentralID PMC3714863

  • Contemporaneous Dual Catalysis by Coupling Highly Transient Nucleophilic and Electrophilic Intermediates Generated in Situ JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Luan, X. 2011; 133 (6): 1706-1709

    Abstract

    We report herein a new process, which we call contemporaneous dual catalysis, that selectively couples two highly reactive catalytic intermediates while overcoming competing trapping by stoichiometric reactive species also present in the reaction. The reaction proceeds via the convergence of a vanadium-catalyzed propargylic rearrangement and a palladium-catalyzed allylic alkylation. It generates a variety of α-allylated α,β-unsaturated ketones, which are not readily accessible by other means. Notably, this dual catalysis is achieved using low catalyst loadings (1.0 mol % [Pd], 1.5 mol % [V]) and gives good to excellent yields (up to 98%) of the desired products.

    View details for DOI 10.1021/ja110501v

    View details for Web of Science ID 000287831800025

    View details for PubMedID 21244050

  • An Atom-Economical Access to beta-Heteroarylated Ketones from Propargylic Alcohols via Tandem Ruthenium/Indium Catalysis ORGANIC LETTERS Trost, B. M., Breder, A. 2011; 13 (3): 398-401

    Abstract

    The direct and chemoselective synthesis of β-heteroarylated ketones from secondary propargyl alcohols through tandem Ru/In catalysis is reported. Both electron-rich and neutral heteroarenes, such as furans and indoles, efficiently undergo the redox isomerization/conjugate addition (RICA) sequence to provide the corresponding adducts in yields of up to 97%.

    View details for DOI 10.1021/ol102706j

    View details for Web of Science ID 000286577600013

    View details for PubMedID 21190354

  • An Atom-Economic Synthesis of Nitrogen Heterocycles from Alkynes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lumb, J., Azzarelli, J. M. 2011; 133 (4): 740-743

    Abstract

    A robust route to 2,4-disubstituted pyrrole heterocycles relying upon a cascade reaction is reported. The reaction benefits from operational simplicity: it is air and moisture tolerant and is performed at ambient temperature. Control over the reaction conditions provides ready access to isopyrroles, 2,3,4-trisubstituted pyrroles, and 3-substituted pyrollidin-2-ones.

    View details for DOI 10.1021/ja110117g

    View details for Web of Science ID 000287295300028

    View details for PubMedID 21175138

    View details for PubMedCentralID PMC3043142

  • Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of beta-ketoesters: An Unusual Counterion Effect ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Schaeffner, B., Osipov, M., Wilton, D. A. 2011; 50 (15): 3548-3551
  • Palladium-Catalyzed Diastereo- and Enantioselective Synthesis of Substituted Cyclopentanes through a Dynamic Kinetic Asymmetric Formal [3+2]-Cycloaddition of Vinyl Cyclopropanes and Alkylidene Azlactones ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Morris, P. J. 2011; 50 (27): 6167-6170

    View details for DOI 10.1002/anie.201101684

    View details for Web of Science ID 000292641200033

    View details for PubMedID 21604344

    View details for PubMedCentralID PMC3407808

  • Synthesis of a tricyclic core of rameswaralide TETRAHEDRON LETTERS Trost, B. M., Nguyen, H. M., Koradin, C. 2010; 51 (48): 6232-6235

    Abstract

    A tricyclic core containing a 5,7-fused bicyclic unit of rameswaralide was prepared starting from a 1,6-enyne. The synthetic sequence involved (i) ruthenium-catalyzed [5+2]-cycloaddition of 1,6-enyne, (ii) an acyl radical based approach to construct the lactone, and (iii) a regioselective installation of the conjugated double bond by a concomitant sulfenylation-dehydrosulfenylation sequence.

    View details for DOI 10.1016/j.tetlet.2010.09.042

    View details for Web of Science ID 000284303200006

    View details for PubMedCentralID PMC2976576

  • Total Synthesis of Bryostatin 16 Using a Pd-Catalyzed Diyne Coupling as Macrocyclization Method and Synthesis of C20-epi-Bryostatin 7 as a Potent Anticancer Agent JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dong, G. 2010; 132 (46): 16403-16416

    Abstract

    Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence and in 39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward this end, 20-epi-bryostatin 7 was synthesized from a bryostatin 16-like intermediate; the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines.

    View details for DOI 10.1021/ja105129p

    View details for Web of Science ID 000284792000031

    View details for PubMedID 21043491

    View details for PubMedCentralID PMC2993185

  • Palladium-Catalyzed Asymmetric Benzylation of 3-Aryl Oxindoles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Czabaniuk, L. C. 2010; 132 (44): 15534-15536

    Abstract

    Herein we report palladium-catalyzed asymmetric benzylic alkylation with 3-aryl oxindoles as prochiral nucleophiles. Proceeding analogously to asymmetric allylic alkylation, asymmetric benzylation occurs in high yield and enantioselectivity for a variety of unprotected 3-aryl oxindoles and benzylic methyl carbonates using chiral bisphosphine ligands. This methodology represents a novel asymmetric carbon-carbon bond formation between a benzyl group and a prochiral nucleophile to generate a quaternary center.

    View details for DOI 10.1021/ja1079755

    View details for Web of Science ID 000283955600026

    View details for PubMedID 20961054

  • Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformations of Vinyl Aziridines with Nitrogen Heterocycles: Rapid Access to Biologically Active Pyrroles and Indoles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Osipov, M., Dong, G. 2010; 132 (44): 15800-15807

    Abstract

    We report that nitrogen heterocycles can serve as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric alkylation of vinyl aziridines. The resulting alkylated products were obtained with high regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this process was demonstrated by applying this method to the preparation of several medicinal chemistry lead compounds and bromopyrrole alkaloids including longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin.

    View details for DOI 10.1021/ja1071509

    View details for Web of Science ID 000283955600065

    View details for PubMedID 20949972

    View details for PubMedCentralID PMC2975595

  • Catalytic asymmetric allylic alkylation employing heteroatom nucleophiles: a powerful method for C-X bond formation CHEMICAL SCIENCE Trost, B. M., Zhang, T., Sieber, J. D. 2010; 1 (4): 427-440

    View details for DOI 10.1039/c0sc00234h

    View details for Web of Science ID 000283480900001

  • Palladium-Catalyzed Asymmetric Allylic Alkylation of 2-Acylimidazoles as Ester Enolate Equivalents JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lehr, K., Michaelis, D. J., Xu, J., Buckl, A. K. 2010; 132 (26): 8915-?

    Abstract

    A broad range of highly enantioenriched 2-acylimidazoles are synthesized by palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of 2-imidazolo-substituted enol carbonates. The enantioenriched 2-acylimidazole products can easily be converted to the corresponding carboxylic acid, ester, amide, and ketone derivatives with complete retention of the enantiopurity. The synthetic utility of this new method is demonstrated in the short, efficient synthesis of cetiedil.

    View details for DOI 10.1021/ja103771w

    View details for Web of Science ID 000279561200045

    View details for PubMedID 20550121

    View details for PubMedCentralID PMC2908042

  • Differential Reactivities of Enyne Substrates in Ruthenium- and Palladium-Catalyzed Cycloisomerizations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Gutierrez, A. C., Ferreira, E. M. 2010; 132 (26): 9206-9218

    Abstract

    Complementary methods for the transition-metal-catalyzed enyne cycloisomerizations of cyclic olefins have been developed. By using distinct ruthenium and palladium catalysts, decalins and 7,6-bicycles can be obtained with dichotomous stereochemical outcomes. The change in mechanism that accompanies the change in metal affords trans-fused 1,4-dienes with ruthenium and their cis-fused diastereomers under palladium catalysis. In the reactions under ruthenium catalysis, a coordinating group is required and acts to direct the metal to the same side of the carbocycle, resulting in the observed trans diastereoselectivity. Subtle changes in the carbocyclic substrate led to the discovery of a heretofore-unobserved mechanistic pathway, providing bicyclic cycloisomerization products under palladium catalysis and tricyclic products under ruthenium catalysis in N,N-dimethylacetamide (DMA). The differential effect of DMA supports a mechanism in which the coordination requirements of the two paths differ, allowing for the reaction to be shuttled through the metallacycle pathway (generating tricyclic products) when DMA is used as a solvent.

    View details for DOI 10.1021/ja103663h

    View details for Web of Science ID 000279561200080

    View details for PubMedID 20545356

    View details for PubMedCentralID PMC2904572

  • Enantioselective Construction of Highly Substituted Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Ketimines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Silverman, S. M. 2010; 132 (24): 8238-?

    Abstract

    The transition-metal catalyzed trimethylenemethane [3+2] cycloaddition provides a direct route to functionalized heterocycles. Herein, we describe a protocol for the reaction between 1-cyano-2-((trimethylsilyl)methyl)allyl acetate and a series of ketimines to generate highly substituted pyrrolidines. This methodology showcases a catalytic, asymmetric addition of a carbon nucleophile to ketimines, examples of which are still rare. The corresponding pyrrolidines were obtained in excellent yields and selectivities making use of our novel phosphoramidite ligands L2-L3.

    View details for DOI 10.1021/ja102102d

    View details for Web of Science ID 000278905700007

    View details for PubMedID 20504020

  • Enantioselective ProPhenol-Catalyzed Addition of 1,3-Diynes to Aldehydes to Generate Synthetically Versatile Building Blocks and Diyne Natural Products JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Chan, V. S., Yamamoto, D. 2010; 132 (14): 5186-5192

    Abstract

    A highly enantioselective method for the catalytic addition of terminal 1,3-diynes to aldehydes was developed using our dinuclear zinc ProPhenol (1) system. Furthermore, triphenylphosphine oxide was found to interact synergistically with the catalyst to substantially enhance the chiral recognition. The generality of this catalytic transformation was demonstrated with aryl, alpha,beta-unsaturated and saturated aldehydes, of which the latter were previously limited in alkynyl zinc additions. The chiral diynol products are also versatile building blocks that can be readily elaborated; this was illustrated through highly selective trans-hydrosilylations, which enabled the synthesis of a beta-hydroxyketone and enyne. Additionally, the development of this method allowed for the rapid total syntheses of several biologically important diynol-containing natural products.

    View details for DOI 10.1021/ja910656b

    View details for Web of Science ID 000276553700048

    View details for PubMedID 20307084

    View details for PubMedCentralID PMC2864593

  • Palladium-catalyzed asymmetric [3+2] methylene-trimethylenemethane cycloaddition reactions Trost, B. M., Maruniak, A. AMER CHEMICAL SOC. 2010
  • A Concise Enantioselective Synthesis of (-)-Ranirestat ORGANIC LETTERS Trost, B. M., Osipov, M., Dong, G. 2010; 12 (6): 1276-1279

    Abstract

    A concise, enantioselective synthesis of the potent aldose reductase inhibitor ranirestat (1) is reported. The synthesis was accomplished employing inexpensive, commercially available starting materials. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to construct the tetrasubstituted chiral center in the target.

    View details for DOI 10.1021/ol100167w

    View details for Web of Science ID 000275379100034

    View details for PubMedID 20148531

    View details for PubMedCentralID PMC2850125

  • Investigation of a Domino Heck Reaction for the Rapid Synthesis of Bicyclic Natural Products CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., O'Boyle, B. M., Hund, D. 2010; 16 (32): 9772-9776

    View details for DOI 10.1002/chem.201001689

    View details for Web of Science ID 000281689700012

    View details for PubMedID 20669198

  • Synthesis of a Tricyclic Core of Rameswaralide. Tetrahedron letters Trost, B. M., Nguyen, H. M., Koradin, C. 2010; 41 (48): 6232–35

    Abstract

    A tricyclic core containing a 5,7-fused bicyclic unit of rameswaralide was prepared starting from a 1,6-enyne. The synthetic sequence involved (i) ruthenium-catalyzed [5+2]-cycloaddition of 1,6-enyne, (ii) an acyl radical based approach to construct the lactone, and (iii) a regioselective installation of the conjugated double bond by a concomitant sulfenylation-dehydrosulfenylation sequence.

    View details for PubMedID 21076637

    View details for PubMedCentralID PMC2976576

  • Catalytic Double Stereoinduction in Asymmetric Allylic Alkylation of Oxindoles CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Zhang, Y. 2010; 16 (1): 296-303

    Abstract

    A highly regio-, diastereo-, and enantioselective allylic alkylation reaction of 3-monosubstituted oxindoles catalyzed by molybdenum is described. The reaction is affected by the electronic and steric variations of the nucleophile. The use of appropriate N-protecting group is particularly important for achieving high regio- and diastereoselectivity. Products from this reaction, containing vicinal quaternary-tertiary stereogenic centers, are valuable synthetic intermediates and should find utility in alkaloid synthesis.

    View details for DOI 10.1002/chem.200902770

    View details for Web of Science ID 000274007900036

    View details for PubMedID 20013766

    View details for PubMedCentralID PMC3488305

  • Cyclic 1,2-Diketones as Core Building Blocks: A Strategy for the Total Synthesis of (-)-Terpestacin CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Dong, G., Vance, J. A. 2010; 16 (21): 6265-6277

    Abstract

    We report a full account of our work towards the total synthesis of (-)-terpestacin (1), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti-HIV and anti-cancer activity, as well as its novel structure, make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2-diketones (diosphenols) was developed and total synthesis of 1 was achieved in 20 steps, in the longest linear sequence, from commercially available 2-hydroxy-3-methyl-2-cyclopenten-1-one. The key feature of our synthesis is the double usage of a "Pd AAA-Claisen" protocol (AAA=asymmetric allylic alkylation), first in the early stages to generate the C1 quaternary center and then in the late stages to install the side chain. In addition, a rather unusual ene-1,2-dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration many interesting chemoselectivity issues have been addressed, such as a highly selective ring-closing metathesis and a challenging oxidation of a disubstituted olefin in the presence of three trisubstituted ones.

    View details for DOI 10.1002/chem.200903356

    View details for Web of Science ID 000278880300019

    View details for PubMedID 20411537

    View details for PubMedCentralID PMC2914478

  • The direct catalytic asymmetric aldol reaction CHEMICAL SOCIETY REVIEWS Trost, B. M., Brindle, C. S. 2010; 39 (5): 1600-1632

    Abstract

    Asymmetric aldol reactions are a powerful method for the construction of carbon-carbon bonds in an enantioselective fashion. Historically this reaction has been performed in a stoichiometric fashion to control the various aspects of chemo-, diastereo-, regio- and enantioselectivity, however, a more atom economical approach would unite high selectivity with the use of only a catalytic amount of a chiral promoter. This critical review documents the development of direct catalytic asymmetric aldol methodologies, including organocatalytic and metal-based strategies. New methods have improved the reactivity, selectivity and substrate scope of the direct aldol reaction and enabled the synthesis of complex molecular targets (357 references).

    View details for DOI 10.1039/b923537j

    View details for Web of Science ID 000277035200015

    View details for PubMedID 20419212

    View details for PubMedCentralID PMC3714873

  • Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Enol Carbonates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xu, J., Schmidt, T. 2009; 131 (51): 18343-18357

    Abstract

    Palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of allyl enol carbonates as a highly chemo-, regio-, and enantioselective process for the synthesis of ketones bearing either a quaternary or a tertiary alpha-stereogenic center has been investigated in detail. Chiral ligand L4 was found to be optimal in the DAAA of a broad scope of cyclic and acyclic ketones including simple aliphatic ketones with more than one enolizable proton. The allyl moiety of the carbonates has been extended to a variety of cyclic or acyclic disubstituted allyl groups. Our mechanistic studies reveal that, similar to the direct allylation of lithium enolates, the DAAA reaction proceeds through an "outer sphere" S(N)2 type of attack on the pi-allylpalladium complex by the enolate. An important difference between the DAAA reaction and the direct allylation of lithium enolates is that in the DAAA reaction, the nucleophile and the electrophile were generated simultaneously. Since the pi-allylpalladium cation must serve as the counterion for the enolate, the enolate probably exists as a tight-ion-pair. This largely prevents the common side reactions of enolates associated with the equilibrium between different enolates. The much milder reaction conditions as well as the much broader substrate scope also represent the advantages of the DAAA reaction over the direct allylation of preformed metal enolates.

    View details for DOI 10.1021/ja9053948

    View details for Web of Science ID 000273615800046

    View details for PubMedID 19928805

    View details for PubMedCentralID PMC2804400

  • Evaluating Transition-Metal-Catalyzed Transformations for the Synthesis of Laulimalide JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Amans, D., Seganish, W. M., Chung, C. K. 2009; 131 (47): 17087-?

    Abstract

    Laulimalide is a structurally unique 20-membered marine macrolide displaying microtubule stabilizing activity similar to that of paclitaxel and the epothilones. The use of atom-economical transformations such as a Rh-catalyzed cycloisomerization to form the endocyclic dihydropyran, a dinuclear Zn-catalyzed asymmetric glycolate aldol reaction to prepare the syn 1,2-diol, and an intramolecular Ru-catalyzed alkene-alkyne coupling to build the macrocycle enabled us to synthesize laulimalide via an efficient and convergent pathway. The designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity.

    View details for DOI 10.1021/ja907924j

    View details for Web of Science ID 000272207300027

    View details for PubMedID 19891433

    View details for PubMedCentralID PMC2791108

  • Total Synthesis and Stereochemical Assignment of (-)-Ushikulide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., O'Boyle, B. M., Hund, D. 2009; 131 (41): 15061-15074

    Abstract

    We report the determination of the full stereostructure of (-)-ushikulide A (1), a spiroketal containing macrolide by total synthesis. Ushikulide A (1) was isolated from a culture broth of Streptomyces sp. IUK-102 and exhibits potent immunosuppressant activity (IC(50) = 70 nM). To embark upon an ushikulide A synthesis, a tentative assignment was made based on analogy to cytovaricin (2), a related macrolide isolated from a culture of Streptomyces diastatochromogenes whose full structure was previously established via synthesis and X-ray crystallography. This report delineates studies on several key steps, namely a direct aldol reaction catalyzed by the dinuclear zinc ProPhenol complex, a metal catalyzed spiroketalization, as well as application of an unprecedented asymmetric alkynylation of a simple saturated aldehyde with methyl propiolate to prepare the nucleophilic partner for a Marshall-Tamaru propargylation. These studies culminated in the first total synthesis and stereochemical assignment of (-)-ushikulide A and significantly extended the scope of the above-mentioned methodologies.

    View details for DOI 10.1021/ja906056v

    View details for Web of Science ID 000271271800083

    View details for PubMedID 19775093

    View details for PubMedCentralID PMC2791109

  • Asymmetric Syntheses of Oxindole and Indole Spirocyclic Alkaloid Natural Products SYNTHESIS-STUTTGART Trost, B. M., Brennan, M. K. 2009: 3003-3025
  • Palladium-Catalyzed Regio-, Diastereo-, and Enantioselective Benzylic Allylation of 2-Substituted Pyridines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Thaisrivongs, D. A. 2009; 131 (34): 12056-?

    Abstract

    We report a new method for the highly regio-, diastereo-, and enantioselective palladium-catalyzed allylic alkylation of 2-substituted pyridines that allows for the formation of homoallylic stereocenters containing alkyl, aryl, heteroaryl, and nitrogen substituents. When the reaction is conducted with asymmetric acyclic electrophiles, both linear and branched products may be obtained exclusively by selecting the appropriate regioisomeric starting material and ligand, an example of the "memory effect." Deuterium-labeling studies reveal that though no such phenomenon occurs with racemic cyclic electrophiles, the chiral ligand employed reacts kinetically faster with the enantiomer of the substrate for which it is "matched" and yet eventually converts all "mismatched" substrate to product.

    View details for DOI 10.1021/ja904441a

    View details for Web of Science ID 000269379600018

    View details for PubMedID 19645450

    View details for PubMedCentralID PMC3235048

  • Access to a Welwitindolinone Core Using Sequential Cycloadditions ORGANIC LETTERS Trost, B. M., McDougall, P. J. 2009; 11 (16): 3782-3785

    Abstract

    A concise approach to the core skeleton of the welwitindolinone alkaloids was developed on the basis of sequential cycloaddition reactions. First, a palladium catalyzed enantioselective [6 + 3] trimethylenemethane cycloaddition onto a tropone nucleus was used to generate the requisite bicyclo[4.3.1]decadiene. Subsequent modifications to the cycloadduct allowed for an intramolecular [4 + 2] cycloaddition to generate the oxindole and complete the core of the natural product family.

    View details for DOI 10.1021/ol901499b

    View details for Web of Science ID 000268796700066

    View details for PubMedID 19606876

    View details for PubMedCentralID PMC2736368

  • Direct N-Carbamoylation of 3-Monosubstituted Oxindoles with Alkyl Imidazole Carboxylates JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Zhang, Y., Zhang, T. 2009; 74 (14): 5115-5117

    Abstract

    Regioselective N-carbamoylation of oxindoles was achieved through the use of imidazole carboxylate reagents. This reaction provides ready access to N-carbamoyl-3-monosubstituted oxindoles.

    View details for DOI 10.1021/jo900760r

    View details for Web of Science ID 000268139700033

    View details for PubMedID 19588998

  • Tandem Ruthenium-Catalyzed Redox Isomerization-O-Conjugate Addition: An Atom-Economic Synthesis of Cyclic Ethers ORGANIC LETTERS Trost, B. M., Gutierrez, A. C., Livingston, R. C. 2009; 11 (12): 2539-2542

    Abstract

    An atom-economical method for the convenient synthesis of tetrahydropyrans and tetrahydrofurans is reported. Enones and enals derived from the [IndRu(PPh(3))(2)Cl]-catalyzed redox isomerization of primary and secondary propargyl alcohols undergo a subsequent intramolecular conjugate addition to provide cyclic ethers in excellent yields.

    View details for DOI 10.1021/ol9007876

    View details for Web of Science ID 000266930900016

    View details for PubMedID 19449896

    View details for PubMedCentralID PMC2728751

  • The Enantioselective Addition of Alkyne Nucleophiles to Carbonyl Groups ADVANCED SYNTHESIS & CATALYSIS Trost, B. M., Weiss, A. H. 2009; 351 (7-8): 963-983
  • Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Hitce, J. 2009; 131 (13): 4572-?

    Abstract

    Under dinuclear catalysis, the direct conjugate addition of 2(5H)-furanone to nitroalkenes involves the gamma-position of the nucleophile. The synthetically versatile Michael adducts are prepared in good yields, with high levels of diastereo- and enantioselectivity. A model is presented to rationalize the observed stereoselectivity.

    View details for DOI 10.1021/ja809723u

    View details for PubMedID 19281239

    View details for PubMedCentralID PMC2679032

  • Asymmetric Synthesis of Diamine Derivatives via Sequential Palladium and Rhodium Catalysis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Malhotra, S., Olson, D. E., Maruniak, A., Du Bois, J. 2009; 131 (12): 4190-?

    Abstract

    The use of a bifunctional nitrogen nucleophile and an allyl carbonate starting material in successive enantioselective palladium- and diastereoselective rhodium-catalyzed reactions enables the rapid assembly of unique amino aziridine products. Further elaboration of these materials affords complex, stereodefined polyamine architectures, thus demonstrating the power of these combined methods for simplifying asymmetric C-N bond construction.

    View details for DOI 10.1021/ja809697p

    View details for Web of Science ID 000264792900010

    View details for PubMedID 19275160

    View details for PubMedCentralID PMC3235049

  • A Regioselective Ru-Catalyzed Alkene-Alkyne Coupling To Form (Z,Z)-1,3-Dienes ORGANIC LETTERS Trost, B. M., Martos-Redruejo, A. 2009; 11 (5): 1071-1074

    Abstract

    Generally, Ru-catalyzed alkene-alkyne coupling forms 1,4-dienes. A version of this process which generates a 1,3-diene as the Z,Z-isomer preferentially has now been observed. The scope of this new atom-economic process is described herein.

    View details for DOI 10.1021/ol8028324

    View details for Web of Science ID 000263776200008

    View details for PubMedID 19193028

  • Magnesium-Catalyzed Asymmetric Direct Aldol Addition of Ethyl Diazoacetate to Aromatic, Aliphatic, and alpha,beta-Unsaturated Aldehydes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Malhotra, S., Fried, B. A. 2009; 131 (5): 1674-?

    Abstract

    Magnesium-catalyzed enantioselective aldol between ethyl diazoacetate and aromatic, aliphatic, and alpha,beta-unsaturated aldehydes affords alpha-diazo-beta-hydroxy-esters in high enantioselectivities. Aldol adducts resulting from this asymmetric transformation are versatile intermediates toward the synthesis of several ester containing chiral building blocks.

    View details for DOI 10.1021/ja809181m

    View details for Web of Science ID 000264792100026

    View details for PubMedID 19191696

    View details for PubMedCentralID PMC2652472

  • Si-Based Benzylic 1,4-Rearrangernent/Cyclization Reaction ORGANIC LETTERS Trost, B. M., Bertogg, A. 2009; 11 (3): 511-513

    Abstract

    The trans-selective hydrosilylation of ynones (1) yields beta-silylated enones (2) that undergo a benzylic 1,4-rearrangement/cyclization reaction in the presence of base, yielding 2,5-dihydro-1,2-oxasiloles (3).

    View details for DOI 10.1021/ol802289f

    View details for Web of Science ID 000262913500004

    View details for PubMedID 19125665

    View details for PubMedCentralID PMC2640427

  • Simple menaquinones reduce carbon tetrachloride and iron (III) BIODEGRADATION Fu, Q. S., Boonchayaanant, B., Tang, W., Trost, B. M., Criddle, C. S. 2009; 20 (1): 109-116

    Abstract

    Cell-free supernatant from Shewanella oneidensis MR-1 reduced carbon tetrachloride to chloroform, a suspension of Fe(III) and solid Fe(III) to iron (II). The putative reducing agent was tentatively identified as menaquinone-1 (MQ-1)-a water-soluble menaquinone with a single isoprenoid residue in the side chain. Synthetic MQ-1 reduced carbon tetrachloride to chloroform and amorphous iron (III) hydroxide to iron (II). To test the generality of this result among menaquinones, the reductive activities of vitamin K(2) (MQ-7)-a lipid-associated menaquinone with 7 or 8 isoprenoid residues-was evaluated. This molecule also reduced carbon tetrachloride to chloroform and iron (III) to iron (II). The results indicate that molecules within the menaquinone family may contribute to both the extracellular and cell-associated reduction of carbon tetrachloride and iron (III).

    View details for DOI 10.1007/s10532-008-9204-4

    View details for Web of Science ID 000262085700011

    View details for PubMedID 18594993

  • Ruthenium-Catalyzed Cross-Coupling of Tertiary Propargyl Alcohols with omega-Alkynenitriles: A Regio- and Stereoselective Surrogate for an Aldol Condensation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Maulide, N., Rudd, M. T. 2009; 131 (2): 420-?

    Abstract

    A novel catalytic alkyne cross-coupling reaction is reported which connects tertiary propargyl alcohols with omega-alkynylnitriles with perfect atom economy. This remarkable process generates highly functionalized, stereodefined dienones that are formal aldol products in a single step. Moreover, the specificity of the cyano substituent for this reaction demonstrates the unique and somewhat underappreciated properties of that functional group.

    View details for DOI 10.1021/ja8077686

    View details for Web of Science ID 000262521800012

    View details for PubMedID 19099475

  • A Stereodivergent Strategy to Both Product Enantiomers from the Same Enantiomer of a Stereoinducing Catalyst: Agelastatin A CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Dong, G. 2009; 15 (28): 6910-6919

    Abstract

    In this article, we report a full account of our recent development of pyrroles and N-alkoxyamides as new classes of nucleophiles for palladium-catalyzed AAA reactions, along with application of these methodologies in the total synthesis of agelastatin A, a marine natural product with exceptional anticancer activity and other biological properties. Our method allows for access to either regioisomer of the pyrrolopiperazinones (6 and 19) with high efficiency and enantioselectivity. Note that isomer 19 was obtained via a cascade reaction through a double allylic alkylation pathway. From regioisomer 6, the total synthesis of (+)-agelastatin A was completed in a very short fashion (four steps from 6), during the course of which we developed a new copper catalyst for aziridination and an In(OTf)(3)/DMSO system to oxidatively open an N-tosyl aziridine. Starting with the other pyrrolopiperazinone 19, a five-step sequence has been developed to furnish a formal total synthesis of (-)-agelastatin A. A unique feature of our syntheses is the use of two rather different strategies for the total syntheses of both enantiomers of agelastatin A using the same enantiomer of a chiral palladium catalyst.

    View details for DOI 10.1002/chem.200900794

    View details for Web of Science ID 000268286200018

    View details for PubMedID 19533707

    View details for PubMedCentralID PMC2914473

  • The Enantioselective Addition of Alkyne Nucleophiles to Carbonyl Groups. Advanced synthesis & catalysis Trost, B. M., Weiss, A. H. 2009; 351 (7-8)

    Abstract

    Over the past decade, large strides have been achieved in the invention of methods for the direct enantioselective addition of alkynes and metal alkynylide nucleophiles into prochiral aldehydes, ketones, and imines. This review highlights and compares the available methods for these transformations.

    View details for PubMedID 24353484

    View details for PubMedCentralID PMC3864370

  • Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Sieber, J. D., Qian, W., Dhawan, R., Ball, Z. T. 2009; 48 (30): 5478-5481

    View details for DOI 10.1002/anie.200901907

    View details for Web of Science ID 000268290400017

    View details for PubMedID 19554583

  • Stereoselective, Dual-Mode Ruthenium-Catalyzed Ring Expansion of Alkynylcyclopropanols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xie, J., Maulide, N. 2008; 130 (51): 17258-?

    Abstract

    A novel, dual-pathway ring expansion of alkynylcyclopropanols is described. On treatment with a ruthenium catalyst, these compounds undergo highly selective enlargement to either (Z)-alkylidene cyclobutanones or beta-substituted cyclopentenones. The unique ability to access the least selective double bond isomers of alkylidene cyclobutanones and the dramatic shift of reactivity observed further illustrate the particular intricacies of ruthenium catalysis when compared to other alkynophilic transition metals.

    View details for DOI 10.1021/ja807894t

    View details for Web of Science ID 000263320600027

    View details for PubMedID 19053484

    View details for PubMedCentralID PMC2655345

  • A Ruthenium-Catalyzed, Atom-Economical Synthesis of Nitrogen Heterocycles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Maulide, N., Livingston, R. C. 2008; 130 (49): 16502-?

    View details for DOI 10.1021/ja807696e

    View details for Web of Science ID 000263320200030

    View details for PubMedID 19554686

    View details for PubMedCentralID PMC2888904

  • Total Synthesis of (-)-Pseudolaric Acid B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Waser, J., Meyer, A. 2008; 130 (48): 16424-16434

    Abstract

    We report a full account of our work toward the total synthesis of pseudolaric acid B (1a), a diterpene acid isolated from the bark of Pseudolarix kaempferi Gordon (pinaceae). Compound 1a is an antifungal and antifertility agent. Furthermore, its capacity for inhibiting tubulin polymerization makes it a potential lead for cancer therapy. Herein, we describe the use of a Ru- or Rh-catalyzed [5 + 2] intramolecular cycloaddition reaction of an alkyne and a vinylcyclopropane for the construction of the polyhydroazulene core of the molecule. Our first unsuccessful strategy for the introduction of the quaternary center based on an epoxide opening with cyanide led to the discovery of a new TBAF-mediated isomerization of a 1,4-diene to a 1,3-diene and a vinylogous eliminative opening of an epoxide to form a dienol. Our second strategy, based on the cyclization of an alkoxycarbonyl radical upon a diene system, succeeded in forming the quaternary center. Detailed studies showed the dependence of this underutilized approach for the synthesis of lactones on substrate structure and reaction conditions. In the late stage of the synthesis, the unique capacity of cerium organometallic reagents to add to a sensitive, sterically hindered ketone was demonstrated. The easy formation of an oxo-bridged derivative was the major hurdle to the completion of the synthesis and showcased the intriguing reactivity of the complex core of the pseudolaric acids.

    View details for DOI 10.1021/ja806724x

    View details for Web of Science ID 000263319800058

    View details for PubMedID 18998641

    View details for PubMedCentralID PMC2698933

  • Ruthenium- and Palladium-Catalyzed Enyne Cycloisomerizations: Differentially Stereoselective Syntheses of Bicyclic Structures JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ferreira, E. M., Gutierrez, A. C. 2008; 130 (48): 16176-?

    Abstract

    Enyne cycloisomerizations can provide an efficient means for forming carbon-carbon bonds. We describe stereoselectively dichotomous enyne cycloisomerizations, entirely dependent on the selection of catalytic manifold. Ruthenium catalysis provides trans-fused bicyclic systems, whereas palladium catalysis provides the analogous cis-fused bicycles. A number of substrates are investigated, and the outcomes ultimately offer a clear mechanistic rationale for these observations.

    View details for DOI 10.1021/ja8078835

    View details for Web of Science ID 000263319800026

    View details for PubMedID 18998647

    View details for PubMedCentralID PMC2665024

  • Exploiting Orthogonally Reactive Functionality: Synthesis and Stereochemical Assignment of (-)-Ushikulide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., O'Boyle, B. M. 2008; 130 (48): 16190-?

    Abstract

    In spite of the tremendous advances in modern spectroscopic methods, organic synthesis continues to play a pivotal role in elucidating the full structures of complex natural products. This method has the advantage that, even in the absence of a firm structural assignment, a combination of logic and spectroscopic comparison can arrive at the correct structure. Herein, we report execution of this strategy with respect to ushikulide A, a newly isolated and previously stereochemically undefined member of the oligomycin-rutamycin family. To maximize synthetic efficiency, we envisioned chemoselective manipulation of orthogonally reactive functional groups, notably alkenes and alkynes as surrogates for certain carbonyl and hydroxyl functionalities. This approach has the dual effect of minimizing the number of steps and protecting groups required for our synthetic route. This strategy culminated in the efficient synthesis and stereochemical assignment of ushikulide A.

    View details for DOI 10.1021/ja807127s

    View details for Web of Science ID 000263319800031

    View details for PubMedID 18989964

    View details for PubMedCentralID PMC2655346

  • Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches NATURE Trost, B. M., Dong, G. 2008; 456 (7221): 485-488

    Abstract

    Of the concepts used to improve the efficiency of organic syntheses, two have been especially effective: atom economy (the use of routes in which most of the atoms present in the reactants also end up in the product) and chemoselectivity (the use of reactions that take place only at desired positions in a molecule). Synthesis of complex natural products is the most demanding arena in which to explore such principles. The bryostatin family of compounds are especially interesting targets, because they combine structural complexity with promising biological activity. Furthermore, synthetic routes to some bryostatins have already been reported, providing a benchmark against which new syntheses can be measured. Here we report a concise total synthesis of bryostatin 16 (1), a parent structure from which almost all other bryostatins could in principle be accessed. Application of atom-economical and chemoselective reactions currently under development provides ready access to polyhydropyran motifs in the molecule, which are common structural features of many other natural products. The most notable transformations are two transition-metal-catalysed reactions. The first is a palladium-catalysed reaction of two different alkynes to form a large ring. The product of this step is then converted into a dihydropyran (the 'C ring' of bryostatins) in the second key reaction, which is catalysed by a gold compound. Analogues of bryostatin that do not exist in nature could be readily made by following this route, which might allow the biological activity of bryostatins to be fine-tuned.

    View details for DOI 10.1038/nature07543

    View details for Web of Science ID 000261170500034

    View details for PubMedID 19037312

    View details for PubMedCentralID PMC2728752

  • Asymmetric Synthesis of Bicyclo[4.3.1]decadienes and Bicyclo[3.3.2]decadienes via [6+3] Trimethylenemethane Cycloaddition with Tropones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., McDougall, P. J., Hartmann, O., Wathen, P. T. 2008; 130 (45): 14960-?

    Abstract

    The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield.

    View details for DOI 10.1021/ja806979b

    View details for Web of Science ID 000260682300029

    View details for PubMedID 18937462

    View details for PubMedCentralID PMC2665030

  • Strategy for Employing Unstabilized Nucleophiles in Palladium-Catalyzed Asymmetric Allylic Alkylations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Thaisrivongs, D. A. 2008; 130 (43): 14092-?

    Abstract

    We report a strategy for the employment of highly unstabilized anions in palladium-catalyzed asymmetric allylic alkylations (AAA). The "hard" 2-methylpyridyl nucleophiles studied are first reacted in situ with BF3.OEt2; subsequent deprotonation of the resulting complexes with LiHMDS affords "soft" anions that are competent nucleophiles in AAA reactions. The reaction is selective for the 2-position of methylpyridines and tolerates bulky aryl and alkyl substitution at the 3-, 4-, and 5-positions. Investigations into the reaction mechanism demonstrate that the configuration of the allylic stereocenter is retained, consistent with the canonical outer sphere mechanism invoked for palladium-catalyzed allylic substitution processes of stabilized anions.

    View details for DOI 10.1021/ja806781u

    View details for Web of Science ID 000260301700036

    View details for PubMedID 18826305

  • An atom-economic and selective ruthenium-catalyzed redox isomerization of propargylic alcohols. An efficient strategy for the synthesis of leukotrienes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Livingston, R. C. 2008; 130 (36): 11970-11978

    Abstract

    Catalytic ruthenium complexes in conjunction with an indium cocatalyst and Bronsted acid isomerize primary and secondary propargylic alcohols in good yields to provide trans enals and enones exclusively. Readily available indenylbis(triphenylphosphine)ruthenium chloride, in the presence of indium triflate and camphorsulfonic acid, gives the best turnover numbers and reactivity with the broadest range of substrates. Deuterium labeling experiments suggest that the process occurs through propargylic hydride migration followed by protic cleavage of the resultant vinylruthenium intermediate. Application of this method to the synthesis of leukotriene B4 demonstrates its utility and extraordinary selectivity.

    View details for DOI 10.1021/ja804105m

    View details for Web of Science ID 000258950500036

    View details for PubMedID 18702463

    View details for PubMedCentralID PMC2562263

  • Ligand controlled highly regio- and enantioselective synthesis of alpha-acyloxyketones by palladium-catalyzed allylic alkylation of 1,2-enediol carbonates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xu, J., Schmidt, T. 2008; 130 (36): 11852-11853

    Abstract

    The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl 1,2-enediol carbonates 1 can decompose to either alpha-hydroxyketones 3 or alpha-hydroxyaldehydes 4. The product distribution is largely controlled by the ligand. Using Lnaph in DME we exclusively obtained the ketone product in good to excellent yields and high enantiomeric excesses. The reaction proceeds under extremely mild conditions, so we can have a broad range of choices of OR. Besides the commonly used protection groups such as OAc and OPiv, a more functionalized group such as methyl but-2-enoyl group can also be used, downstream process of which can afford other synthetically interesting structures.

    View details for DOI 10.1021/ja8038954

    View details for Web of Science ID 000258950500009

    View details for PubMedID 18710230

    View details for PubMedCentralID PMC2711528

  • Coupling of alkenes and alkynes: Synthesis of the C1-C11 and C18-C28 fragments of miyakolide ORGANIC LETTERS Trost, B. M., Ashfeld, B. L. 2008; 10 (10): 1893-1896

    Abstract

    A transition metal-mediated, atom-economical approach toward the crucial A and D rings of miyakolide is described. A Pd-catalyzed alkyne-alkyne coupling/6- endo- dig cyclization is employed to assemble the A ring fragment. The key D ring pyran is constructed utilizing an Ru-catalyzed alkene-alkyne coupling followed by a Pd-catalyzed allylic alkylation to establish the all-cis stereochemistry.

    View details for DOI 10.1021/ol800347u

    View details for Web of Science ID 000255694100004

    View details for PubMedID 18426220

  • Palladium-catalyzed diastereo- and enantioselective Wagner-Meerwein shift: Control of absolute stereochemistry in the C-C bond migration event JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Me, J. 2008; 130 (19): 6231-6242

    Abstract

    Inducing absolute stereochemistry in Wagner-Meerwein shifts was examined in a ring expansion protocol. Initiated by generation of a pi-allylpalladium intermediate by hydropalladation of allenes, the ring expansion of allenylcyclobutanol substrates proceeded with excellent diastereo- and enantioselectivities. The results demonstrate that, during the C-C bond migration process, our chiral catalysts can control the stereochemistry of both the pi-allylpalladium intermediate and the corresponding migration bond. Moreover, the stereochemical outcome of the reaction can be rationalized very well with the working model of the chiral catalyst. The method provides an efficient way to synthesize highly substituted cyclopentanones with an alpha-chiral O-tertiary center which has various synthetic applications.

    View details for DOI 10.1021/ja7111299

    View details for Web of Science ID 000255620200029

    View details for PubMedID 18429612

  • Synthesis of 7-Epi (+)-FR900482: An epimer of comparable anti-cancer activity ORGANIC LETTERS Trost, B. M., O'Boyle, B. M. 2008; 10 (7): 1369-1372

    Abstract

    FR900482 is a potent anti-tumor therapeutic that has been investigated as a replacement candidate for the clinically useful Mitomycin C. Herein, we report synthesis and biological testing of 7-Epi (+)-FR900482, which demonstrates equal potency relative to the natural product against several cancer cell lines. Highlights of this work include utilization of our palladium-catalyzed DYKAT methodology and development of a Polonovski oxidative ring expansion strategy to yield this equipotent epimer in 23 linear steps.

    View details for DOI 10.1021/ol800127a

    View details for Web of Science ID 000254489900012

    View details for PubMedID 18318539

  • Asymmetric Friedel-Crafts alkylation of pyrroles with nitroalkenes using a dinuclear zinc catalyst JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Mueller, C. 2008; 130 (8): 2438-2439

    View details for DOI 10.1021/ja711080y

    View details for Web of Science ID 000253400900033

    View details for PubMedID 18237176

  • Dinuclear zinc-catalyzed asymmetric desymmetrization of acyclic 2-substituted-1,3-propanediols: A powerful entry into chiral building blocks CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Malhotra, S., Mino, T., Rajapaksa, N. S. 2008; 14 (25): 7648-7657

    Abstract

    The asymmetric acylation of meso-2-substituted-1,3-propanediols by using an amphoteric chiral dinuclear zinc catalyst is described. It is has been demonstrated that both 2-alkyl- and 2-aryl-1,3-propanediols can be desymmetrized in high yields and enantioselectivities by using the same family of ligands. Given that both antipodes of the chiral catalyst are available, both enantiomers of the desymmetrized product can be obtained from the same starting material. The synthetic utility of the desymmetrized products has been demonstrated by the synthesis of several chiral building blocks with high enantiomeric purities.

    View details for DOI 10.1002/chem.200800623

    View details for Web of Science ID 000259079400029

    View details for PubMedID 18655088

    View details for PubMedCentralID PMC2199377

  • Metal vinylidenes as catalytic species in organic reactions CHEMISTRY-AN ASIAN JOURNAL Trost, B. M., McClory, A. 2008; 3 (2): 164-194

    Abstract

    Organic vinylidene species have found limited use in organic synthesis owing to their inaccessibility. In contrast, metal vinylidenes are much more stable and may be readily accessed through transition-metal activation of terminal alkynes. These electrophilic species may be trapped by a number of nucleophiles. Additionally, metal vinylidenes can participate in pericyclic reactions and processes that involve migration of a metal ligand to the vinylidene species. This Focus Review addresses the reactions and applications of metal vinylidenes in organic synthesis.

    View details for DOI 10.1002/asia.200700247

    View details for Web of Science ID 000253130300002

    View details for PubMedID 18172846

    View details for PubMedCentralID PMC2483426

  • A concise synthesis of (-)-oseltamivir ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Zhang, T. 2008; 47 (20): 3759-3761

    View details for DOI 10.1002/anie.200800282

    View details for Web of Science ID 000255791200017

    View details for PubMedID 18399551

  • Mo-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of 3-aryloxindoles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Zhang, Y. 2007; 129 (47): 14548-?

    Abstract

    A highly regio-, diastereo-, and enantioselective allylic alkylation reaction mediated by a chiral molybdenum catalyst has been developed as a novel entry into synthetically versatile 3-alkyl-3-aryloxindoles. Extremely bulky nucleophiles were employed to form a quaternary center and an adjacent tertiary center asymmetrically concurrently. The regio- and diastereoselectivity of the reaction is dependent upon the steric and electronic nature of the nucleophiles to an unusual degree. A reaction mechanism based on the bonding modes of molybdenum enolate complexes was discussed.

    View details for DOI 10.1021/ja0755717

    View details for PubMedID 17985899

    View details for PubMedCentralID PMC2536500

  • Total synthesis of (-)-pseudolaric acid B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Waser, J., Meyer, A. 2007; 129 (47): 14556-?

    Abstract

    We report the enantioselective synthesis of pseudolaric acid B (1a), a diterpene acid isolated from the bark of Pseudolarix kaempferi Gordon, which displays interesting antifungal, antifertility, and cytotoxic activity against multidrug resistant cell lines. Our synthesis utilizes a highly efficient metal-catalyzed [5 + 2] vinylcyclopropane-alkyne intramolecular cycloaddition to construct the polyhydroazulene core of the natural product. Elaboration to the tricyclic scaffold of the pseudolaric acids was completed with an intramolecular alkoxycarbonyl radical cyclization to form the quaternary center and a highly diastereoselective cerium acetylide addition to a methyl ketone for introduction of the acid side chain.

    View details for DOI 10.1021/ja076165q

    View details for Web of Science ID 000251142200014

    View details for PubMedID 17985906

    View details for PubMedCentralID PMC2535803

  • The O-acylation of ketone enolates by allyl 1H-imidazole-1-carboxylate mediated with boron trifluoride etherate - A convenient procedure for the synthesis of substituted allyl enol carbonates JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Xu, J. 2007; 72 (24): 9372-9375

    Abstract

    A convenient access to substituted allyl enol carbonates was established through the reaction of ketone enolates with the complex of allyl 1H-imidazole-1-carboxylates and boron trifluoride etherate.

    View details for DOI 10.1021/jo7016313

    View details for Web of Science ID 000251039700052

    View details for PubMedID 17963405

    View details for PubMedCentralID PMC2587353

  • Enantioselective construction of spirocyclic oxindolic Cyclopentanes by palladium-catalyzed trimethylenemethane-[3+2]-cycloaddition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Cramer, N., Silverman, S. M. 2007; 129 (41): 12396-?

    View details for DOI 10.1021/ja075335w

    View details for Web of Science ID 000250105500028

    View details for PubMedID 17880222

    View details for PubMedCentralID PMC2615581

  • Palladium-catalyzed asymmetric [3+2] cycloaddition of trimethylenemethane with Imines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Silverman, S. M., Stambuli, J. P. 2007; 129 (41): 12398-?

    View details for DOI 10.1021/ja0753389

    View details for Web of Science ID 000250105500029

    View details for PubMedID 17887679

    View details for PubMedCentralID PMC2532588

  • Palladium-catalyzed regio- and enantioselective allylic alkylation of Bis allylic carbonates derived from Morita-Baylis-Hillman adducts ORGANIC LETTERS Trost, B. M., Brennan, M. K. 2007; 9 (20): 3961-3964

    Abstract

    Morita-Baylis-Hillman diene adducts are used as substrates in the palladium-catalyzed asymmetric allylic alkylation reaction with oxygen and carbon nucleophiles in good regio- and enantioselectivity.

    View details for DOI 10.1021/o1701585b

    View details for Web of Science ID 000249697800026

    View details for PubMedID 17803313

  • Total synthesis of (+)-frondosin A. Application of the Ru-catalyzed [5+2] cycloaddition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Hu, Y., Horne, D. B. 2007; 129 (38): 11781-11790

    Abstract

    The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.

    View details for DOI 10.1021/ja073272b

    View details for Web of Science ID 000249693800028

    View details for PubMedID 17760442

  • ORGN 929-Palladium-catalyzed diastereoselective and enantioselective Wagner-Meerwein shift: Ring expansion of allenylcyclobutanols Xie, J., Trost, B. M. AMER CHEMICAL SOC. 2007
  • Total synthesis of spirotryprostatin B via diastereoselective prenylation ORGANIC LETTERS Trost, B. M., Stiles, D. T. 2007; 9 (15): 2763-2766

    Abstract

    Spirotryprostatin B was synthesized in eight steps, utilizing an efficient palladium-catalyzed prenylation reaction to construct the quaternary C3 stereocenter. The decarboxylation-alkylation of a series of substituted beta-keto esters is described, demonstrating the broad scope of this class of pronucleophiles and allylating agents.

    View details for DOI 10.1021/ol070971k

    View details for Web of Science ID 000247966400003

    View details for PubMedID 17592853

  • Asymmetric annulation toward pyrrolopiperazinones: Concise enantioselective syntheses of pyrrole alkaloid natural products ORGANIC LETTERS Trost, B. M., Dong, G. 2007; 9 (12): 2357-2359

    Abstract

    A novel Pd-catalyzed asymmetric annulation between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines has been developed to efficiently construct pyrrolopiperazinones, which can serve as key intermediates in the enantioselective syntheses of pyrrole alkaloid natural products. In this paper, the total synthesis of (-)-longamide B in five steps and the first total syntheses of agesamides A and B in six steps from 6 and 7 are reported.

    View details for DOI 10.1021/ol070742y

    View details for Web of Science ID 000246842600028

    View details for PubMedID 17497869

  • Dinuclear zinc-catalyzed enantioselective aza-Henry reaction ORGANIC LETTERS Trost, B. M., Lupton, D. W. 2007; 9 (10): 2023-2026

    Abstract

    The dinuclear zinc catalyst 1a was found to catalyze the addition of nitroalkanes to carbamate-protected imines. This aza-Henry reaction proceeds with high enantioselectivity when various carbamate-protected imines are used. alpha,beta-Unsaturated imines proved to be a particularly useful class of substrate routinely giving the alpha-nitro amine products in high enantiomeric excess.

    View details for DOI 10.1021/ol070618e

    View details for Web of Science ID 000246190800046

    View details for PubMedID 17439228

  • A diosphenol-based strategy for the total synthesis of (-)-terpestacin JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dong, G., Vance, J. A. 2007; 129 (15): 4540-?

    View details for DOI 10.1021/ja070571s

    View details for Web of Science ID 000245739700018

    View details for PubMedID 17343388

  • Ruthenium-catalyzed cycloisomerization-6 pi-cyclization: A novel route to pyridines ORGANIC LETTERS Trost, B. M., Gutierrez, A. C. 2007; 9 (8): 1473-1476

    Abstract

    [reaction: see text] Herein we report a method for the synthesis of substituted pyridines. The unsaturated ketones and aldehydes derived from the cycloisomerization of primary and secondary propargyl diynols in the presence of [CpRu(CH3CN)3]PF6 (1) are converted to 1-azatrienes which in turn undergo a subsequent electrocyclization-dehydration to provide pyridines with excellent regiocontrol.

    View details for DOI 10.1021/ol070163t

    View details for Web of Science ID 000245439000013

    View details for PubMedID 17362020

    View details for PubMedCentralID PMC2678947

  • Concise total synthesis of (+/-)-marcfortine B JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Cramer, N., Bernsmann, H. 2007; 129 (11): 3086-?

    View details for DOI 10.1021/ja070142u

    View details for Web of Science ID 000244896900028

    View details for PubMedID 17315880

  • Synthesis of (-)-Delta(9)-trans-Tetrahydrocannabinol: Stereocontrol via Mo-catalyzed asymmetric allylic alkylation reaction ORGANIC LETTERS Trost, B. M., Dogra, K. 2007; 9 (5): 861-863

    Abstract

    [reaction: see text] Delta9-THC is synthesized in enantiomericaly pure form, where all of the stereochemistry is derived from the molybdenum-catalyzed asymmetric alkylation reaction of the extremely sterically congested bis-ortho-substituted cinnamyl carbonate in high regio- and enantioselectivity.

    View details for DOI 10.1021/ol063022k

    View details for Web of Science ID 000244348900032

    View details for PubMedID 17266321

    View details for PubMedCentralID PMC2597621

  • Synthesis of a ring-expanded bryostatin analogue JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Yang, H., Thiel, O. R., Frontier, A. J., Brindle, C. S. 2007; 129 (8): 2206-?

    View details for DOI 10.1021/ja067305j

    View details for Web of Science ID 000244330800004

    View details for PubMedID 17279751

    View details for PubMedCentralID PMC2533160

  • Enantioselective synthesis of alpha-tertiary hydroxyaldehydes by palladium-catalyzed asymmetric allylic alkylation of enolates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xu, J., Reichle, M. 2007; 129 (2): 282-283

    View details for DOI 10.1021/ja067342a

    View details for Web of Science ID 000243381200020

    View details for PubMedID 17212401

    View details for PubMedCentralID PMC2533583

  • Palladium-catalyzed dynamic kinetic asymmetric allylic alkylation with the DPPBA ligands ALDRICHIMICA ACTA Trost, B. M., Fandrick, D. R. 2007; 40 (3): 59-72
  • A convergent Pd-catalyzed asymmetric allylic alkylation of dl- and meso-divinylethylene carbonate: Enantioselective synthesis of (+)-australine hydrochloride and formal synthesis of isoaltholactone CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Aponick, A., Stanzl, B. N. 2007; 13 (34): 9547-9560

    Abstract

    The use of a mixture of dl- and meso-divinylethylene carbonate as an electrophile in palladium-catalyzed asymmetric allylic alkylation reactions is reported. From the diastereomeric mixture of meso and chiral racemic starting materials, a single product is obtained in high optical purity employing either oxygen or nitrogen nucleophiles. The resulting dienes have proven to be versatile synthetic intermediates as each carbon is functionalized for further transformation and differentiated by virtue of the reaction. A mechanism for this intriguing transformation is proposed and a concise enantioselective total synthesis of (+)-australine hydrochloride is reported as well as a formal synthesis of isoaltholactone.

    View details for Web of Science ID 000251391000013

    View details for PubMedID 17847148

  • Rhodium-catalyzed cycloisomerization: Formation of indoles, benzofurans, and enol lactones ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., McClory, A. 2007; 46 (12): 2074-2077

    View details for DOI 10.1002/anie.200604183

    View details for Web of Science ID 000245071000029

    View details for PubMedID 17285670

  • An alkyne strategy for the asymmetric synthesis of natural products: Application to (+)-spirolaxine methyl ether ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Weiss, A. H. 2007; 46 (40): 7664-7666

    View details for DOI 10.1002/anie.200702637

    View details for Web of Science ID 000250249300027

    View details for PubMedID 17722127

  • Dynamic kinetic asymmetric allylic amination and acyl migration of vinyl Aziridines with imido carboxylates ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Tandrick, D. R., Brodmann, T., Stiles, D. T. 2007; 46 (32): 6123-6125

    View details for DOI 10.1002/anie.200700835

    View details for Web of Science ID 000248931100019

    View details for PubMedID 17623279

  • A heterodinuclear asymmetric catalyst for conjugate additions of alpha-hydroxyketones beta-substituted nitroalkenes ORGANIC LETTERS Trost, B. M., Hisaindee, S. 2006; 8 (26): 6003-6005

    Abstract

    [Structure: see text] The bis-ProPhenol ligand was designed to facilitate formation of hetereodinuclear complexes based upon the large difference in pKa of the one phenolic OH group to the tertiary OH groups. In exploring the first example of hydroxyacetophenones as donors in asymmetric Michael reactions with nitroalkene acceptors, the best stereocontrol was observed with a zinc/magnesium dinuclear complex where enantiomeric excesses ranged up to 92% for the major anti diastereomer.

    View details for DOI 10.1021/ol062485n

    View details for Web of Science ID 000242825200022

    View details for PubMedID 17165915

  • Asymmetric synthesis of alpha-substituted aldehydes by Pd-catalyzed asymmetric allylic alkylation-alkene isomerization-Claisen rearrangement ORGANIC LETTERS Trost, B. M., Zhang, T. 2006; 8 (26): 6007-6010

    Abstract

    [Structure: see text] Enantiospecific aliphatic Claisen rearrangement was realized with generally high chirality transfer. The requisite substrates were synthesized via Pd-catalyzed asymmetric allylic alkylation (AAA) from easily obtained starting materials. After protection, the resultant bisallyl ethers underwent olefin isomerization and in situ Claisen rearrangement (ICR) to generate alpha-chiral aldehydes. Remarkable chemoselectivity in the olefin isomerization step was observed. An asymmetric synthesis of communiol A was accomplished applying this methodology.

    View details for DOI 10.1021/ol0624878

    View details for Web of Science ID 000242825200023

    View details for PubMedID 17165916

  • Palladium-catalyzed asymmetric [3+2] trimethylenemethane cycloaddition reactions JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Stambuli, J. P., Silverman, S. M., Schworer, U. 2006; 128 (41): 13328-13329

    Abstract

    Transition-metal-catalyzed trimethylenemethane (TMM) [3 + 2] cycloadditions provide direct routes to functionalized cyclopentanes. This reaction has been shown to be a highly chemo-, regio-, and diastereoselective process. We report a palladium-catalyzed asymmetric [3 + 2] trimethylenemethane (TMM) cycloaddition between 3-acetoxy-2-trimethylsilylmethyl-1-propene and various di- and trisubstituted olefins. Yields of exo-methylenecyclopentane products range from 59 to 99%, and enantiomeric excesses range from 58 to 92% ee.

    View details for DOI 10.1021/ja0640750

    View details for Web of Science ID 000241157600006

    View details for PubMedID 17031924

    View details for PubMedCentralID PMC2535802

  • Predicting the stereochemistry of diphenylphosphino benzoic acid (DPPBA)-based palladium-catalyzed asymmetric allylic alkylation reactions: A working model ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M., Machacek, M. R., Aponick, A. 2006; 39 (10): 747-760

    Abstract

    Palladium-catalyzed asymmetric allylic alkylation has proven to be a powerful method for the preparation of a wide variety of chiral compounds and the rapid assembly of complex molecular architecture from simple starting materials. While many types of catalyst systems have been successfully employed with certain systems, diphenylphosphino benzoic acid (DPPBA) based ligands have found use over a broad range of substrate classes. This Account highlights the mechanistic aspects considered when designing reactions with DPPBA-based ligands and presents a working model for the a priori prediction of their stereochemical outcome.

    View details for DOI 10.1021/ar040063c

    View details for Web of Science ID 000241325500008

    View details for PubMedID 17042475

  • Catalytic enantioselective synthesis of adociacetylene B ORGANIC LETTERS Trost, B. M., Weiss, A. H. 2006; 8 (20): 4461-4464

    Abstract

    A catalytic enantioselective total synthesis of adociacetylene B (2) in five steps is reported. The efficiency of this synthesis was enabled by an asymmetric zinc alkynylation catalyzed by the proline-derived ligand (1).

    View details for DOI 10.1021/ol0615836

    View details for Web of Science ID 000240654700020

    View details for PubMedID 16986925

  • ORGN 262-Palladium-catalyzed asymmetric Wagner-Meerwein Shift: Ring expansion of allenylcyclobutanols Trost, B. M., Xie, J. AMER CHEMICAL SOC. 2006
  • Synthesis of substituted 1,3-diene synthetic equivalents by a Ru-catalyzed diyne hydrative cyclization CHEMISTRY-AN ASIAN JOURNAL Trost, B. M., Huang, X. 2006; 1 (3): 469-478

    Abstract

    Catalyzed by [CpRu(CH3CN)3]PF6, the hydrative cyclization of dipropargylic sulfone substrates provides an effective way to synthesize highly functionalized substituted 3-sulfolenes. The amount of water is crucial for the reactivity of this cycloisomerization reaction. The scope and limitations of the Ru-catalyzed cycloisomerization are discussed. A marked ketone-directing effect was observed for the first time in ruthenium-catalyzed cyclizations. A plausible mechanism for the ketone-directed cycloisomerization is also rationalized. The utility of this method was demonstrated by both sulfur dioxide extrusion of the 3-sulfolenes to afford 1,3-dienes and subsequent inter- or intramolecular Diels-Alder reactions.

    View details for DOI 10.1002/asia.200600109

    View details for Web of Science ID 000243223000020

    View details for PubMedID 17441084

  • Palladium-catalyzed DYKAT of butadiene monoepoxide: Enantioselective total synthesis of (+)-DMDP, (-)-bulgecinine, and (+)-broussonetine G CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Horne, D. B., Woltering, M. J. 2006; 12 (25): 6607-6620

    Abstract

    Palladium catalyzed asymmetric allylic alkylation reaction of an amine with two equivalents of butadiene monoxide allows for the expedient synthesis of trans- and cis-2,5-dihydropyrroles. The versatility of these chiral synthons towards the synthesis of a wide variety of iminosugar natural products was demonstrated with the short and high yielding asymmetric syntheses of (+)-DMDP, and (-)-bulgecinine. In addition, the first total synthesis of (+)-broussonetine G, a potent glycosidase inhibitor, is described along with the assignment of its relative and absolute stereochemical configuration.

    View details for DOI 10.1002/chem.200600202

    View details for Web of Science ID 000240358200016

    View details for PubMedID 16807949

  • Ruthenium-catalyzed alkylative lactonization and carbocyclization ORGANIC LETTERS Trost, B. M., McClory, A. 2006; 8 (17): 3627-3629

    Abstract

    [reaction: see text] The cationic ruthenium complex [CpRu(NCCH3)3]PF6 promotes the coupling of monosubstituted allene carboxylic acids and simple alpha,beta-unsaturated olefins to form five- and six-membered lactones. The mild reaction conditions allow for the presence of various functional groups.

    View details for DOI 10.1021/ol0610136

    View details for Web of Science ID 000239655500002

    View details for PubMedID 16898777

  • Vanadium-catalyzed addition of propargyl alcohols and imines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Chung, C. K. 2006; 128 (32): 10358-10359

    Abstract

    A Mannich-type addition of propargylic alcohols and N-methoxycarbonylimines has been achieved by using a vanadium catalyst. The reactivity of the vanadium catalyst could be modulated by modifying the silanol ligands to avoid the background reaction. The strategy described herein provides an atom-economical access to beta-aryl-substituted Z-enones with an allylic amino functional group, which are not readily accessible with other methods.

    View details for DOI 10.1021/ja064011p

    View details for Web of Science ID 000239618700006

    View details for PubMedID 16895388

    View details for PubMedCentralID PMC2529155

  • Sequential Ru-Pd catalysis: A two-catalyst one-pot protocol for the synthesis of N- and O-heterocycles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Machacek, M. R., Faulk, B. D. 2006; 128 (20): 6745-6754

    Abstract

    An atom economic, selective, and highly practical two-metal one-pot synthesis of heterocycles has been developed that efficiently affords enantio- and diastereopure N- and O-heterocyclic products. Furthermore, use of a chiral catalyst in the two-metal procedure allows formation of all possible diastereomers, even those that are traditionally difficult to access via cyclization routes due to thermodynamics. Interestingly, the nature of the enantiodiscriminating event differs between the use of amine versus alcohol nucleophiles. The method also affords heterocyclic products that are synthetically useful intermediates. Through the Z-vinylsilane a variety of stereodefined trisubstituted olefin products can be accessed including several all-carbon motifs. Finally, the utility of these heterocyclic products in total synthesis is demonstrated through concise syntheses of a kainoid intermediate, a constituent of oil of rose, and the ring B portion of bryostatin, a potent chemotherapeutic.

    View details for DOI 10.1021/ja060812g

    View details for Web of Science ID 000237590500050

    View details for PubMedID 16704278

    View details for PubMedCentralID PMC2728748

  • Palladium-catalyzed enantioselective C-3 allylation of 3-substituted-1H-indoles using trialkylboranes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Quancard, J. 2006; 128 (19): 6314-6315

    Abstract

    We have developed a new enantioselective C-3 allylation of 3-substituted indoles using allyl alcohol and trialkylboranes. Asymmetric syntheses of 3,3-disubstituted indolines and indolenines in enantiomeric excesses up to 90% have been achieved using the bulky borane 9-BBN-C6H13 as the promoter of the reaction. The dependence of the selectivity on the nature of the borane suggests that the boron reagent has a role beyond promoting ionization of the allyl alcohol. A protocol for oxidation of indolenines to oxindoles has also been developed and led to a formal synthesis of (-)-phenserine.

    View details for DOI 10.1021/ja0608139

    View details for Web of Science ID 000237590400023

    View details for PubMedID 16683785

    View details for PubMedCentralID PMC2516200

  • Palladium asymmetric allylic alkylation of prochiral nucleophiles: Horsfiline ORGANIC LETTERS Trost, B. M., Brennan, M. K. 2006; 8 (10): 2027-2030

    Abstract

    [reaction; see text] The asymmetric synthesis of the oxindole alkaloid horsfiline is described. A palladium-catalyzed asymmetric allylic alkylation (AAA) is used to set the spiro(pyrrolidine-oxindole) stereogenic center.

    View details for DOI 10.1021/ol060298j

    View details for Web of Science ID 000237420200017

    View details for PubMedID 16671773

    View details for PubMedCentralID PMC2565574

  • New class of nucleophiles for palladium-catalyzed asymmetric allylic alkylation. Total synthesis of agelastatin A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dong, G. 2006; 128 (18): 6054-6055

    Abstract

    New classes of nucleophiles, pyrroles, and N-methoxyamides were developed for Pd-catalyzed AAA reactions. By varying the functional groups at the 2-position of pyrroles, either regioisomer of the piperazinone is available. Using one regioisomer, the total synthesis of (+)-agelastatin A in 10 total steps is accomplished. For this synthesis, a new copper-catalyzed aziridination and an indium-catalyzed oxidative ring opening of a N-tosylaziridine were developed. The feasibility of accessing (-)-agelastatin A from the same enantiomer of the chiral catalyst from the other regioisomeric piperazinone is indicated.

    View details for DOI 10.1021/ja061105q

    View details for Web of Science ID 000237468900036

    View details for PubMedID 16669672

    View details for PubMedCentralID PMC2585983

  • Palladium-catalyzed asymmetric ring expansion of allenylcyclobutanols: An asymmetric Wagner-Meerwein shift JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xie, J. 2006; 128 (18): 6044-6045

    Abstract

    In this study, we developed a palladium-catalyzed atom economic asymmetric Wagner-Meerwein shift of allenylcyclobutanol substrates. It is an excellent method for creating functionalized cyclopentanones with an alpha-chiral O-tertiary center by ring expansion of allenylcyclobutanols. This reaction was initiated by hydropalladation and afforded excellent enantioselectivity as well as atom economy. This method provides an efficient route toward the synthesis of natural products such as trans-kumausyne's family, spiro ring systems. In addition, we obtained excellent diastereoselectivity and enantioselectivity at the same time by using 3-monosubstituted allenylcyclobutanol.

    View details for DOI 10.1021/ja0602501

    View details for Web of Science ID 000237468900031

    View details for PubMedID 16669667

    View details for PubMedCentralID PMC2585988

  • Molybdenum-catalyzed asymmetric allylation of 3-alkyloxindoles: Application to the formal total synthesis of (-)-physostigmine JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Zhang, Y. 2006; 128 (14): 4590-4591

    Abstract

    The first example of Mo-catalyzed asymmetric allylation for the generation of quaternary stereocenters at a prochiral nucleophile is reported. A variety of 3-alkyl oxindoles can be alkylated with high yields and enantioselectivity. This method provides expedited access to (-)-physostigmine and its analogues.

    View details for DOI 10.1021/ja060560j

    View details for Web of Science ID 000236770300047

    View details for PubMedID 16594693

  • Palladium-catalyzed asymmetric allylic alkylation of meso- and dl-1,2-divinylethylene carbonate JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Aponick, A. 2006; 128 (12): 3931-3933

    Abstract

    The palladium-catalyzed asymmetric allylic alkylation of a 1:1 mixture of dl- and meso-1,2-divinylethylene carbonate is reported. For the first time, both the ionization and nucleophilic addition steps of the catalytic cycle act as enantiodiscriminating steps to give a single product in high enantiomeric excess. The reactions proceed in >98% ee to efficiently generate useful chiral building blocks from acrolein. The absolute and relative configurations of iso-cladospolide B and 11-epi-iso-cladospolide B were verified by total synthesis, solving an apparent discrepancy in the literature.

    View details for DOI 10.1021/ja0578348

    View details for Web of Science ID 000236401600041

    View details for PubMedID 16551099

    View details for PubMedCentralID PMC2531165

  • Total synthesis of (-)-Frondosin A 231st National Meeting of the American-Chemical-Society Hu, Y., Trost, B. M. AMER CHEMICAL SOC. 2006
  • A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: Synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Jaratjaroonphong, J., Reutrakul, V. 2006; 128 (9): 2778-2779

    Abstract

    The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.

    View details for Web of Science ID 000235942000010

    View details for PubMedID 16506738

  • Palladium-catalyzed chemo- and enantioselective oxidation of allylic esters and carbonates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Richardson, J., Yong, K. 2006; 128 (8): 2540-2541

    Abstract

    The palladium-catalyzed oxidation of allylic esters and carbonates using a novel potassium nitronate has been developed. This method is highly chemoselective, leaving other esters, alcohols, thioethers, and amines undisturbed. The oxidation can be operated in two modes: an achiral mode, using either PPh3 or rac-2 as ligand, or a chiral and highly enantioselective mode, using 2 as ligand. The oxidative enantioselective desymmetrization of meso bis-esters provides a significantly shorter method to arrive at commonly used synthetic intermediates compared to other strategies. Highly efficient kinetic resolution is also possible using this methodology.

    View details for DOI 10.1021/ja057163d

    View details for Web of Science ID 000235787200019

    View details for PubMedID 16492030

    View details for PubMedCentralID PMC2531164

  • S,O-acetals as novel "chiral aldehyde" equivalents CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Crawley, M. L., Lee, C. B. 2006; 12 (8): 2171-2187

    Abstract

    Palladium-catalyzed asymmetric allylic alkylations (AAA) to form "chiral aldehyde" equivalents were investigated. Alpha-acetoxysulfones were formed in high enantiomeric excess as single regioisomers in AAA reactions of allylic geminal dicarboxylates with sodium benzenesulfinate. The directing ability of this novel functional group was highlighted by a series of dihydroxylations, affording syn diols exclusively anti to the acetoxy sulfone as single diastereomers in excellent yields. This is the first example of an asymmetric dihydroxylation protocol that gives the equivalent of reaction with a simple enal. The synthetic value of this process was exemplified by subsequent transformations of the diols including the development of a one-pot dihydroxylation-deprotective acyl migration protocol to give differentially protected 1,2-diols.

    View details for DOI 10.1002/chem.200500919

    View details for Web of Science ID 000236090400007

    View details for PubMedID 16402397

  • Catalytic enantioselective construction of all-carbon quaternary stereocenters SYNTHESIS-STUTTGART Trost, B. M., Jiang, C. H. 2006: 369-396
  • Dinuclear Zn-catalyzed asymmetric alkynylation of unsaturated aldehydes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Weiss, A. H., Jacobi von Wangelin, A. 2006; 128 (1): 8-9

    Abstract

    Our recent development of a proline-derived bimetallic catalyst has led to a number of efficient, catalytic, enantioselective transformations. Herein, we report a practical and general alkynylation of aromatic and alpha,beta-unsaturated aldehydes using our zinc catalyst system.

    View details for DOI 10.1021/ja054871q

    View details for Web of Science ID 000234547700004

    View details for PubMedID 16390095

    View details for PubMedCentralID PMC2596613

  • Asymmetric allylic alkylation of cyclic vinylogous esters and thioesters by Pd-catalyzed decarboxylation of enol carbonate and beta-ketoester substrates ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Bream, R. N., Xu, J. 2006; 45 (19): 3109-3112

    View details for DOI 10.1002/anie.200504421

    View details for Web of Science ID 000237533400017

    View details for PubMedID 16596689

  • Ru-catalyzed alkene-alkyne coupling. Total synthesis of amphidinolide P JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Papillon, J. P., Nussbaumer, T. 2005; 127 (50): 17921-17937

    Abstract

    A coordinatively unsaturated ruthenium complex catalyzed the formation of a carbon-carbon bond between two judiciously chosen alkene and alkyne partners in good yield, and in a chemo- and regioselective fashion, despite the significant degree of unsaturation of the substrates. The resulting 1,4-diene forms the backbone of the cytotoxic marine natural product amphidinolide P. The alkene partner was rapidly assembled from (R)-glycidyl tosylate, which served as a linchpin in a one-flask, sequential three-components coupling process using vinyllithium and a vinyl cyanocuprate. The synthesis of the alkyne partner made use of an unusual anti-selective addition under chelation-control conditions of an allyltin reagent derived from tiglic acid. In addition, a remarkably E-selective E2 process using the azodicarboxylate-triphenylphosphine system is featured. Also featured is the first example of the use of a beta-lactone as a thermodynamic spring to effect macrolactonization. The oxetanone ring was thus used as a productive protecting group that increased the overall efficiency of this total synthesis. This work was also an opportunity to further probe the scope of the ruthenium-catalyzed alkene-alkyne coupling, in particular using enynes, and studies using various functionalized substrates are described.

    View details for DOI 10.1021/ja055967n

    View details for Web of Science ID 000234008900062

    View details for PubMedID 16351124

    View details for PubMedCentralID PMC2533515

  • Alkyne hydrosilylation catalyzed by a cationic ruthenium complex: Efficient and general trans addition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T. 2005; 127 (50): 17644-17655

    Abstract

    The complex [Cp*Ru(MeCN)3]PF6 is shown to catalyze the hydrosilylation of a wide range of alkynes. Terminal alkynes afford access to alpha-vinylsilane products with good regioselectivity. Deuterium labeling studies indicate a clean trans addition process is at work. The same complex is active in internal alkyne hydrosilylation, where absolute selectivity for the trans addition process is maintained. Several internal alkyne substrate classes, including propargylic alcohols and alpha,beta-alkynyl carbonyl compounds, allow regioselective vinylsilane formation. The tolerance of a wide range of silanes is noteworthy, including alkyl-, aryl-, alkoxy-, and halosilanes. This advantage is demonstrated in the direct synthesis of triene substrates for silicon-tethered intramolecular Diels-Alder cycloadditions.

    View details for DOI 10.1021/ja0528580

    View details for Web of Science ID 000234008900032

    View details for PubMedID 16351094

    View details for PubMedCentralID PMC2532823

  • Palladium-catalyzed asymmetric allylic alpha-alkylation of acyclic ketones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xu, J. Y. 2005; 127 (49): 17180-17181

    Abstract

    The first example of Pd-catalyzed asymmetric allyl alkylation of the conformationally nonrigid acyclic ketone enolates is reported with excellent yields, regioselectivity, and enantioselectivity. The double bond geometry of the allyl enol carbonates affects its reactivity, selectivity, as well as the absolute configuration of the products. An opposite enantioselectivity from what is predicted by a direct attack of the enolate on the allyl moiety of the pi-ally-Pd complex was observed. An alternative mechanism was proposed, which involves an inner sphere process of coordination of the enolate to Pd followed by reductive elimination.

    View details for DOI 10.1021/ja055968f

    View details for Web of Science ID 000233917500026

    View details for PubMedID 16332054

    View details for PubMedCentralID PMC2533158

  • Palladium catalyzed ring opening of isoprene monoxide with nitrogen nucleophiles - Asymmetric synthesis of branched amino sugars SYNTHESIS-STUTTGART Trost, B. M., Jiang, C. H., Hammer, K. 2005: 3335-3345
  • Enantioselective palladium-catalyzed addition of 1,3-dicarbonyl compounds to an allene derivative CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Simas, A. B., Plietker, B., Jakel, C., Xie, J. 2005; 11 (23): 7075-7082

    Abstract

    Enhancing atom economy of the metal-catalyzed asymmetric allylic alkylation (AAA) shifts from the usual nucleophilic displacement of a leaving group to an addition of a pronucleophile to a double bond. Using 1-alkoxyallenes as proelectrophiles, the palladium-catalyzed AAA proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regioselectivity and enantiomeric excess under optimized conditions. The pH of the medium proved crucial for reactivity/selectivity. By using the more acidic Meldrum's acids, the reactions required a co-catalytic amount of Brønsted acid, such as trifluoroacetic acid. Single regioisomeric products of 82-99 % ee were obtained. On the other hand, the less acidic 1,3-diketones failed to react under such conditions. The fact that a less acidic acid like benzoic acid sufficed, suggested the need for general base catalysis as well. Thus, a mixture of triethylamine and benzoic acid proved optimal (ee's 93-99). Employment of the (R,R)-phenyl Trost ligand gave a product with S configuration. A model to rationalize the results has been developed.

    View details for DOI 10.1002/chem.200500826

    View details for Web of Science ID 000233508800027

    View details for PubMedID 16196061

  • Selective synthesis of functionalized, tertiary silanes by diastereoselective rearrangement-addition ORGANIC LETTERS Trost, B. M., Ball, Z. T., Kang, E. J. 2005; 7 (22): 4911-4913

    Abstract

    [reaction: see text] Treatment of hydroxy-substituted silyl epoxides with Grignard reagents induces a 1,2-carbon shift to reveal alpha-silyl aldehydes, which are trapped by highly diastereoselective addition reactions of the Grignard reagent. The starting epoxides are readily accessible from propargylic alcohols by regio- and diastereoselective hydrosilylation and epoxidation reactions. In addition to providing functionalized tertiary silane products, the method is shown to offer a tertiary olefin synthesis through chemo- and diastereoselective Peterson elimination of the product tertiary silane diols.

    View details for DOI 10.1021/ol0518636

    View details for Web of Science ID 000232817700032

    View details for PubMedID 16235920

    View details for PubMedCentralID PMC2509579

  • Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Tang, W. P., Toste, F. D. 2005; 127 (42): 14785-14803

    Abstract

    An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.

    View details for DOI 10.1021/ja054449+

    View details for Web of Science ID 000232780900055

    View details for PubMedID 16231933

  • Dynamic kinetic asymmetric allylic alkylations of allenes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Fandrick, D. R., Dinh, D. C. 2005; 127 (41): 14186-14187

    Abstract

    The dynamic kinetic asymmetric allylic alkylations of racemic allene acetates has been developed with the DACH-phenyl Trost ligand 2 to give general access to allenes with high enantiomeric excess (84-95%) for both malonate and amine nucleophiles. Further, a most unusual dependence of enantioselectivity on base has been uncovered. The magnitude of the enantioselectivity is heavily dependent on the base for the malonate nucleophiles, but the sense and magnitude of the asymmetric induction is dependent on the base for the amine nucleophiles. A Rh(I)-catalyzed intramolecular [4 + 2] cycloaddition of the DYKAT products was accomplished to afford formal Diels-Alder adducts, wherein the axial chirality is faithfully transferred into multiple stereogenic centers as well as olefin geometry.

    View details for DOI 10.1021/ja0543705

    View details for Web of Science ID 000232605600033

    View details for PubMedID 16218604

  • A Ru-catalyzed tandem alkyne-enone coupling/Michael addition: Synthesis of 4-methylene-2,6-cis-tetrahydropyrans ORGANIC LETTERS Trost, B. M., Yang, H. B., Wuitschik, G. 2005; 7 (21): 4761-4764

    Abstract

    [reaction: see text] A Ru-catalyzed tandem alkyne-enone coupling/Michael addition reaction is reported. It provides an efficient, atom-economic entry to 4-methylene-2,6-cis-tetrahydropyrans from simple, readily available homopropargylic alcohols and beta,gamma-unsaturated enones in good yields. Further functionalization of the resultant vinylsilane leads to the synthesis of either geometrically defined trisubstituted alkene exocyclic to the 2,6-cis-dihydropyran.

    View details for DOI 10.1021/ol0520065

    View details for Web of Science ID 000232506700054

    View details for PubMedID 16209529

  • Total synthesis of (+)-amphidinolide A. Structure elucidation and completion of the synthesis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Harrington, P. E., Chisholm, J. D., Wrobleski, S. T. 2005; 127 (39): 13598-13610

    Abstract

    The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. The 20-membered ring of amphidinolide A was formed by a ruthenium-catalyzed alkene-alkyne coupling to forge the C15-C16 bond. Using the reported structure 1 as a starting point, a number of diastereomers of amphidinolide A were prepared. Deviations of the chemical shift of key protons in each isomer relative to the natural material were used as a guide to determine the locations of the errors in the relative stereochemistry. The spectroscopic data for the synthetic and natural material are in excellent agreement.

    View details for DOI 10.1021/ja053365y

    View details for Web of Science ID 000232257100049

    View details for PubMedID 16190725

  • Total synthesis of (+)-amphidinolide A. Assembly of the fragments JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Wrobleski, S. T., Chisholm, J. D., Harrington, P. E., Jung, M. 2005; 127 (39): 13589-13597

    Abstract

    The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.

    View details for DOI 10.1021/ja0533646

    View details for Web of Science ID 000232257100048

    View details for PubMedID 16190724

  • Exploiting the Pd- and Ru-catalyzed cycloisomerizations: Enantioselective total synthesis of (+)-allocyathin B-2 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dong, L., Schroeder, G. M. 2005; 127 (29): 10259-10268

    Abstract

    Pd- and Ru-catalyzed cycloisomerizations of 1,6-enynes are compared and contrasted. Such considerations led to the enantioselective synthesis of a cyathin terpenoid, (+)-allocyathin B(2) (1). The synthesis features a Pd-catalyzed asymmetric allylic alkylation (AAA) to install the initial quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. We demonstrate for the first time a mechanism-based stereochemical divergence in Pd- and Ru-catalyzed cycloisomerization reactions as well as in creation of alkene geometry with alkynes bearing a carboalkoxy group. Mechanistic rationalization is proposed for these observations.

    View details for DOI 10.1021/ja051547m

    View details for Web of Science ID 000230700700042

    View details for PubMedID 16028937

    View details for PubMedCentralID PMC2565572

  • An alkyne hydrosilylation-oxidation strategy for the selective installation of oxygen functionality JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T., Laemmerhold, K. M. 2005; 127 (28): 10028-10038

    Abstract

    Alkynes bearing propargylic, homopropargylic, and bishomopropargylic hydroxyl groups are shown to serve as precursors for ketone or alpha-hydroxy ketone functionality. The approach hinges on the intermediacy of vinylsilanes created through regioselective hydrosilylation catalyzed by the complex [Cp*Ru(MeCN)3]PF6. Several oxidative pathways of linear and cyclic vinylsilanes are studied, and the possibility of diastereoselective epoxidation of cyclic vinylsilanes is demonstrated. The sequences constitute the equivalent of stereoselective aldol, homo-aldol, and bishomo-aldol type processes. The method is applied to a short synthesis of the piperidine alkaloid, spectaline.

    View details for DOI 10.1021/ja051578h

    View details for PubMedID 16011365

    View details for PubMedCentralID PMC2581901

  • Direct asymmetric Zn-aldol reaction of methyl vinyl ketone and its synthetic applications JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Shin, S. H., Sclafani, J. A. 2005; 127 (24): 8602-8603

    Abstract

    A direct catalytic asymmetric aldol reaction of methyl vinyl ketone is described using our dinuclear zinc catalyst. The obtained aldol adduct functions as a bifunctional building block by utilization of the vinyl functionality. For example, convergent fragment coupling methods have been demonstrated via highly diastereoselective cycloaddition of nitrile oxide after reduction into 1,3-diol or via cross-metathesis reaction.

    View details for DOI 10.1021/ja0511526s

    View details for Web of Science ID 000229981200011

    View details for PubMedID 15954759

    View details for PubMedCentralID PMC2535804

  • Synthesis of allenamides by copper-catalyzed coupling of allenyl halides with amides, carbamates, and ureas ORGANIC LETTERS Trost, B. M., Stiles, D. T. 2005; 7 (11): 2117-2120

    Abstract

    [reaction: see text]. A variety of N-substituted allenes have been synthesized by the copper-catalyzed coupling reaction between allenyl halides and amides, carbamates, and ureas. The reactions proceed in good to excellent yield using 7 mol % copper thiophenecarboxylate and 15 mol % of a diamine catalyst.

    View details for DOI 10.1021/ol050395x

    View details for Web of Science ID 000229420400010

    View details for PubMedID 15901148

  • Ruthenium-catalyzed diyne hydrative cyclization: Synthesis of substituted 1,3-diene synthons ORGANIC LETTERS Trost, B. M., Huang, X. J. 2005; 7 (11): 2097-2099

    Abstract

    [reaction: see text]. A novel and versatile strategy for the synthesis of highly functionalized substituted 3-sulfolenes based on [CpRu(CH3CN)3]PF6-catalyzed hydrative cyclization has been developed. A marked ketone directing effect in ruthenium-catalyzed cyclization was observed for the first time. This provides complementary chemoselectivity for the synthesis of 3-sulfolenes and other cyclic enones. The utility of this method has been demonstrated by SO2 extrusion of 3-sulfolenes to afford 1,3-dienes and the subsequent inter- and intramolecular Diels-Alder reaction.

    View details for DOI 10.1021/ol0502937

    View details for Web of Science ID 000229420400005

    View details for PubMedID 15901143

  • Development of aliphatic alcohols as nucleophiles for palladium-catalyzed DYKAT reactions: Total synthesis of (+)-hippospongic acid A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Machacek, M. R., Tsui, H. C. 2005; 127 (19): 7014-7024

    Abstract

    The ability to use aliphatic alcohols as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric transformation of Baylis-Hillman adducts is explored. High yield and enantioselectivity is obtained for both the kinetic transformation and dynamic kinetic transformation. The absolute stereochemistry of the products is used to explore the reactive conformation of 2-substituted pi-allyl complexes with DPPBA-based chiral ligands. The utility of this method is further demonstrated in the context of a concise total synthesis of the gastrulation inhibitor (+)-hippospongic acid A. The synthesis features three palladium-catalyzed allylic alkylation reactions to introduce three different bond types: C-S, C-H, and C-O.

    View details for DOI 10.1021/ja050340q

    View details for Web of Science ID 000229085200036

    View details for PubMedID 15884945

  • Addition of metalloid hydrides to alkynes: Hydrometallation with boron, silicon, and tin SYNTHESIS-STUTTGART Trost, B. M., Ball, Z. T. 2005: 853-887
  • Syntheses of seven-membered rings: Ruthenium-catalyzed intramolecular [5+2] cycloadditions Symposium on Chemistry-A European Conference - Stimulating Concepts in Chemistry Trost, B. M., Shen, H. C., Horne, D. B., Toste, E. D., Steinmetz, B. G., Koradin, C. WILEY-V C H VERLAG GMBH. 2005: 2577–90

    Abstract

    The Ru-catalyzed intramolecular [5+2] cycloaddition of cyclopropylenynes is investigated with respect to the regio- and diastereoselectivity as well as the functional group compatibility of the reaction. Evidence for the mechanism as occurring through a ruthenacyclopentene intermediate is elucidated from 1) the study of the diastereoselectivity of the cycloaddition; 2) the effect of variation of substituents on the regioselectivity of cyclopropyl bond cleavage in 1,2-trans- and 1,2-cis-disubstituted cyclopropanes and 3) examples that clearly do not involve ruthenacyclohexene as intermediates as products still incorporate the cyclopropyl moiety. The scope and limitations of the Ru-catalyzed cycloaddition are discussed and compared with the Rh-catalyzed reaction. The potential power of this methodology towards natural product total synthesis is demonstrated by the formation of several polycyclic systems with the chosen reaction conditions and readily available cyclopropylenyne substrates.

    View details for DOI 10.1002/chem.200401065

    View details for Web of Science ID 000228412500030

    View details for PubMedID 15736147

  • Ruthenium-catalyzed cycloisomerizations of diynols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rudd, M. T. 2005; 127 (13): 4763-4776

    Abstract

    A wide variety of diynols containing tertiary, secondary, and primary propargylic alcohols undergo a cycloisomerization reaction to form dienones and dienals in the presence of a catalytic amount of [CpRu(CH(3)CN)(3)]PF(6). The formation of five- and six-membered rings is possible using this methodology. Secondary diynols react to form single geometrical isomeric dienones and -als. Primary diynols undergo a cycloisomerization as well as a hydrative cyclization process. The utility of primary diynol cycloisomerization is demonstrated in a synthesis of (+)-alpha-kainic acid.

    View details for DOI 10.1021/ja043097o

    View details for Web of Science ID 000228089300045

    View details for PubMedID 15796542

  • Dinuclear asymmetric Zn aldol additions: Formal asymmetric synthesis of fostriecin JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Frederiksen, M. U., Papillon, J. P., Harrington, P. E., Shin, S., Shireman, B. T. 2005; 127 (11): 3666-3667

    Abstract

    Direct asymmetric aldol reactions constitute a powerful methodology for the efficient synthesis of complex natural products. Herein we report the first application of our recently reported dinuclear Zn-catalyzed direct aldol addition of alkynyl ketones to aldehydes in a short and efficient formal asymmetric synthesis of fostriecin, a potent cyctotoxic natural product. This work highlights not only the power of the aldol methodology but also the utility of the akynyl silane aldol adducts, as it is subsequently utilized in a vinyl silane cross-coupling reaction which affords the target molecule in 14 steps for the longest linear sequence in 8.5% overall yield.

    View details for DOI 10.1021/ja042435i

    View details for Web of Science ID 000227738700011

    View details for PubMedID 15771479

  • Total synthesis of (+)-allocyathin B-2 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dong, L., Schroeder, G. M. 2005; 127 (9): 2844-2845

    Abstract

    The first enantioselective synthesis of (+)-allocyathin was achieved. The synthesis features a Pd-catalyzed asymmetric allylic alkylation to install the first quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. The unusual olefin isomerization of the Ru-catalyzed cycloisomerization was discussed and exploited for the synthesis.

    View details for DOI 10.1021/ja0435586

    View details for Web of Science ID 000227479600025

    View details for PubMedID 15740107

  • Regio- and enantioselective Pd-catalyzed allylic alkylation of ketones through allyl enol carbonates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Xu, J. Y. 2005; 127 (9): 2846-2847

    Abstract

    The Pd-catalyzed reorganization of enol allyl carbonates to allylated ketones occurs asymmetrically in the presence of chiral ligands previously developed in this group. With 2-methylcyclohexanone, asymmetric regioselective alkylation occurs at the more substituted carbon without complications of polyalkylation. Alkylation to create quaternary centers in indanones and benzonabenone occurs in much higher ee than using tin or lithium enolates. The sense of enantioinduction in tetralones is opposite from the tin and lithium enolate examples. For the first time, asymmetric creation of tertiary centers occurs with high ee (78-99%). The different results between this reaction and the use of lithium or tin enolates suggest different mechanisms may be involved.

    View details for DOI 10.1021/ja043472c

    View details for Web of Science ID 000227479600026

    View details for PubMedID 15740108

  • Enantioselective synthesis of cyanohydrins by a novel aluminum catalyst SYNLETT Trost, B. M., Martinez-Sanchez, S. 2005: 627-630
  • DYKAT of vinyl aziridines: total synthesis of (+)-pseudodistomin D ORGANIC LETTERS Trost, B. M., Fandrick, D. R. 2005; 7 (5): 823-826

    Abstract

    A concise total synthesis of (+)-pseudodistomin D was developed. The absolute stereochemistry was established through a dynamic kinetic asymmetric cycloaddition of an isocyanate to a vinyl aziridine. The piperidine core was constructed through a silver(I)-catalyzed hydroamination of an alkyne and subsequent diastereo- and regioselective reduction. [reaction: see text]

    View details for DOI 10.1021/ol047513l

    View details for Web of Science ID 000227313400019

    View details for PubMedID 15727450

  • A short and concise asymmetric synthesis of hamigeran B CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Pissot-Soldermann, C., Chen, I. 2005; 11 (3): 951-959

    Abstract

    The interesting biological properties of the hamigerans wherein hamigeran B is a potent antiviral agent with low cytotoxicity to host cells make these deceptively simple looking structures challenging synthetic targets. A strategy to hamigeran B evolved wherein the three contiguous stereocenters are established ultimately from a Pd catalyzed asymmetric allylic alkylation (AAA). The latter involves an asymmetric allylation of a non-stabilized ketone enolate in 77 % yield and 93 % ee. By using this process, (S)-5-allyl-2-isopropyl-5-methyl-1-trifluoromethanesulfonyloxycyclopentene becomes available in four steps from 2-methylcyclopentanone. Introduction of the aryl unit by cross-coupling proceeded intermolecularly but failed intramolecularly. On the other hand, reductive removal of the triflate permitted a Heck reaction to effect intramolecular introduction of the aryl ring. The unusual conformational properties of this molecular architecture are revealed by the regioselectivity of the beta-hydrogen elimination in the Heck reaction and the diastereoselectivity of the reduction establishing the stereochemistry of the carbon bearing the isopropyl group. The successful route consists of 15 steps from 2-methylcyclopentanone and dimethylorcinol illustrating the efficiency of the route based upon the Pd AAA.

    View details for DOI 10.1002/chem.200400558

    View details for Web of Science ID 000226714400017

    View details for PubMedID 15612053

  • Ruthenium-catalyzed reactions - A treasure trove of atom-economic transformations ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Frederiksen, M. U., Rudd, M. T. 2005; 44 (41): 6630-6666

    Abstract

    The demand for new chemicals spanning the fields of health care to materials science combined with the pressure to produce these substances in an environmentally benign fashion pose great challenges to the synthetic chemical community. The maximization of synthetic efficiency by the conversion of simple building blocks into complex targets remains a fundamental goal. In this context, ruthenium complexes catalyze a number of non-metathesis conversions and allow the rapid assembly of complex molecules with high selectivity and atom economy. These complexes often exhibit unusual reactivity. Careful consideration of the mechanistic underpinnings of the transformations can lead to the design of new reactions and the discovery of new reactivity.

    View details for DOI 10.1002/anie.200500136

    View details for Web of Science ID 000232958100003

    View details for PubMedID 16206300

  • Palladium-catalyzed asymmetric allylation of prochiral nucleophiles: Synthesis of 3-allyl-3-aryl oxindoles ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Frederiksen, M. U. 2005; 44 (2): 308-310
  • Palladium-catalyzed asymmetric allylic alkylation of ketone enolates CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Schroeder, G. M. 2005; 11 (1): 174-184
  • Palladium-catalyzed asymmetric allylation of prochiral nucleophiles: synthesis of 3-allyl-3-aryl oxindoles. Angewandte Chemie (International ed. in English) Trost, B. M., Frederiksen, M. U. 2004; 44 (2): 308-310

    View details for PubMedID 15614905

  • Palladium-catalyzed asymmetric allylic alkylation of ketone enolates. Chemistry (Weinheim an der Bergstrasse, Germany) Trost, B. M., Schroeder, G. M. 2004; 11 (1): 174-184

    Abstract

    Palladium-catalyzed asymmetric allylic alkylation of nonstabilized ketone enolates to generate quaternary centers has been achieved in excellent yield and enantioselectivity. Optimized conditions consist of performing the reaction in the presence of two equivalents of LDA as base, one equivalent of trimethytin chloride as a Lewis acid, 1,2-dimethoxyethane as the solvent, and a catalytic amount of a chiral palladium complex formed from pi-allyl palladium chloride dimer 3 and cyclohexyldiamine derived chiral ligand 4. Linearly substituted, acyclic 1,3-dialkyl substituted, and unsubstituted allylic carbonates function well as electrophiles. A variety of alpha-tetralones, cyclohexanones, and cyclopentanones can be employed as nucleophiles. The absolute configuration generated is consistent with the current model in which steric factors control stereofacial differentiation. The quaternary substituted products available by this method are versatile substrates for further elaboration.

    View details for PubMedID 15515094

  • Ruthenium-catalyzed enyne cycloisomerizations. Effect of allylic silyl ether on regioselectivity JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Surivet, J. P., Toste, F. D. 2004; 126 (47): 15592-15602

    Abstract

    The ruthenium-catalyzed cycloisomerization of 1,6- and 1,7-enynes substituted in the terminal allylic position with a tert-butyldimethylsilyl ether group emerges as an effective reaction to form unprecedented five- or six-membered rings possessing a geometrically defined enol silane. Straightforward synthetic access to a variety of achiral 1,6- and 1,7-enynes, as well as chiral ones, is presented. Ruthenium catalysts effect efficiently such single-step cycloisomerization at room temperature in acetone under neutral conditions. The cycloisomerization functions with (E) or (Z) 1,2-disubstituted alkenes. Parameters influencing the enol silane geometry are discussed. The level of selectivity depends on the alkyne substitution, the geometry of the double bond, and the nature of the catalyst. Furthermore, examples of stereoinduction are shown and lead to highly substituted carbo- and heterocycles with excellent diastereocontrol.

    View details for DOI 10.1021/ja046824o

    View details for Web of Science ID 000225349800065

    View details for PubMedID 15563189

  • A flexible approach toward trans-fused polycyclic tetrahydropyrans. A synthesis of prymnesin and yessotoxin units ORGANIC LETTERS Trost, B. M., Rhee, Y. H. 2004; 6 (23): 4311-4313

    Abstract

    Ru-catalyzed cycloisomerization and oxidative cyclization of bis-homopropargylic alcohols provide a rapid iterative approach to structural units of the ladder toxins.

    View details for DOI 10.1021/ol048165q

    View details for Web of Science ID 000224973100045

    View details for PubMedID 15524471

  • Regioselectivity control in a ruthenium-catalyzed cycloisomerization of diyne-ols ORGANIC LETTERS Trost, B. M., Rudd, M. T., Costa, M. G., Lee, P. I., Pomerantz, A. E. 2004; 6 (23): 4235-4238

    Abstract

    The ruthenium-catalyzed cycloisomerization of diynes containing one silyl alkyne and one propargyl alcohol yields 2-silyl-[6H]-pyrans instead of the expected unsaturated acylsilanes except when additional conjugation of a aromatic ring is present at the delta-position. Under certain conditions, a facile ruthenium-catalyzed isomerization of the product takes place as well. This regioselectivity of the cyclization can be controlled by the choice of solvent system. DFT calculations confirm the expected greater stability of the silyl-pyrans relative to the acylsilanes.

    View details for DOI 10.1021/ol048351w

    View details for PubMedID 15524451

  • Synthetic stitching with silicon: Geminal alkylation-hydroxylation of alkynyl carbonyl compounds JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T. 2004; 126 (43): 13942-13944

    Abstract

    A new strategy for the synthesis of beta-carbonyl-substituted tertiary alcohols from alpha,beta-alkynyl ketones and esters has been demonstrated. A silicon tether is used to internally deliver an alkyl group, which, combined with a C-Si to C-O transformation, can regio- and diastereoselectively "stitch" together geminal C-C and C-O bonds at the beta-position of an electron-withdrawing group. Regioselective alkyne hydrosilylation by a trans addition process provides clean access to trisubstituted vinylsilanes. Subsequent one-pot fluoride-induced C-C bond formation and oxidation of the resulting tertiary silane, a type of silane not normally reactive to such conditions, affords the desired products. The utility of neighboring ketone and carboxylate groups in promoting the oxidation of these highly hindered tertiary alcohols, an observation that may affect synthetic design of routes depending on such oxidations, is demonstrated. Good diastereoselection (>10:1) is observed for substrates bearing gamma-alkoxy stereocenters.

    View details for DOI 10.1021/ja045971j

    View details for Web of Science ID 000224873600033

    View details for PubMedID 15506753

  • Alkene-alkyne coupling as a linchpin: An efficient and convergent synthesis of amphidinolide P JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Papillon, J. P. 2004; 126 (42): 13618-13619

    Abstract

    A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene-alkyne coupling allows for a convergent synthesis and demonstrates that both enynes and beta-lactones are suitable coupling partners. This work also features a novel strategy for the preparation of macrolactones via intramolecular transesterification of beta-lactones. The target structure was prepared in 15 steps for the longest linear sequence and 10% overall yield, 24 steps total.

    View details for DOI 10.1021/ja045449x

    View details for Web of Science ID 000224685200029

    View details for PubMedID 15493910

  • Biomimetic enantioselective total synthesis of (-)-siccanin via the Pd-catalyzed asymmetric allylic alkylation (AAA) and sequential radical cyclizations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Shen, H. C., Surivet, J. P. 2004; 126 (39): 12565-12579

    Abstract

    (-)-Siccanin (1), a natural product possessing significant antifungal properties, was synthesized enantioselectively via a biomimetic route. This synthetic route features two sequential radical cyclizations: a Ti(III)-mediated radical cyclization of epoxyolefin 48 to construct the B-ring, and a Suarez reaction to establish the tetrahyrofuran ring. Chiral chroman moiety of siccanin was prepared based on our recent development of the Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol trisubstituted allyl carbonates. Several other members of the siccanin family were also synthesized including siccanochromenes A (2), B (3), E (6), F (7), and the methyl ether of siccanochromene C (55). These studies may shed light on the biosynthesis of this novel family of compounds.

    View details for DOI 10.1021/ja048084p

    View details for Web of Science ID 000224219900076

    View details for PubMedID 15453789

  • Synthesis of chiral chromans by the Pd-catalyzed asymmetric allylic alkylation (AAA): Scope, mechanism, and applications JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Shen, H. C., Dong, L., Surivet, J. P., Sylvain, C. 2004; 126 (38): 11966-11983

    Abstract

    The Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol allyl carbonates serves as an efficient strategy to construct the allylic C-O bond allowing access to chiral chromans in up to 98% ee. The effect of pH and the influence of olefin geometry, as well as substitution pattern on the ee and the absolute configuration of the chiral chromans were explored in detail. These observations suggest a mechanism involving the cyclization of the more reactive pi-allyl palladium diastereomeric intermediate as the enantiodiscriminating step (Curtin-Hammett conditions). This methodology led to the enantioselective synthesis of the vitamin E core, the first enantioselective total synthesis of (+)-clusifoliol and (-)-siccanin, and the synthesis of an advanced intermediate toward (+)-rhododaurichromanic acid A.

    View details for DOI 10.1021/ja0480748t

    View details for Web of Science ID 000224103900049

    View details for PubMedID 15382932

  • Asymmetric allylic alkylation, an enabling methodology JOURNAL OF ORGANIC CHEMISTRY Trost, B. M. 2004; 69 (18): 5813-5837

    Abstract

    The diversity of mechanisms for enantiodiscrimination and of bond types that can be formed make Pd-catalyzed asymmetric allylic alkylation a powerful key step for simplification of synthetic strategy to complex molecular targets. Using a wide range of different classes of compounds including alkaloids, polyhydrofurans, nucleosides and carbanucleosides, cyclohexitols and cyclopentitols, chromanes, cyclopentanoids, amino acids, barbiturates, etc., novel synthetic strategies emerge that provide short efficient asymmetric syntheses.

    View details for DOI 10.1021/jo0491004

    View details for Web of Science ID 000223573100001

    View details for PubMedID 15373468

  • Pd-catalyzed carbonylative lactamization: A novel synthetic approach to FR900482 ORGANIC LETTERS Trost, B. M., Ameriks, M. K. 2004; 6 (11): 1745-1748

    Abstract

    An asymmetric synthesis of the benzazocine core of FR900482 has been achieved in 15 steps from 3,5-dinitro-p-toluic acid. Key features of the synthesis include an enantioselective N-methylephedrine-mediated zinc acetylide addition to a highly enolizable arylacetaldehyde and a novel Pd-catalyzed carbonylative lactamization to form an eight-membered ring. [reaction--see text]

    View details for DOI 10.1021/ol049583y

    View details for Web of Science ID 000221567200015

    View details for PubMedID 15151404

  • A "Chiral aldehyde" equivalent as a building block towards biologically active targets CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Crawley, M. L. 2004; 10 (9): 2237-2252

    Abstract

    Chiral gamma-aryloxybutenolides, readily accessible through dynamic kinetic asymmetric transformation (DYKAT) of racemic acyloxybutenolides, were utilized as "chiral aldehyde" building blocks for intermolecular cycloadditions and Michael reactions. Unprecedented selectivity in trimethylenemethane cycloadditions with this building block allowed an efficient synthesis of a novel metabotropic glutamate receptor 1 antagonist in development by the Bayer corporation. These studies further inspired work that culminated in the total synthesis of (+)-brefeldin A, a natural product with a range of significant biological properties. All of the stereochemistry in this target molecule was derived from two palladium-catalyzed asymmetric allylic alkylation reactions. The trans-alkenes were synthesized by a Julia olefination and a ruthenium-catalyzed trans-hydrosilylation-protodesilylation protocol. The route to (+)-brefeldin A lends itself to analogue syntheses and was completed in 18 steps in 6 % overall yield.

    View details for DOI 10.1002/chem.200305634

    View details for Web of Science ID 000221275300015

    View details for PubMedID 15112213

  • Structure elucidation of (+)-amphidinolide A by total synthesis and NMR chemical shift analysis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Harrington, P. E. 2004; 126 (16): 5028-5029

    Abstract

    The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. Using the reported structure as a starting point, a number of diastereomers of amphidinolide A were prepared. The deviations of the chemical shifts of key protons in each isomer relative to the values reported for the isolated material were used to determine the locations of the errors in relative stereochemistry. The spectroscopic data for our proposed structure of (+)-amphidinolide A and the isolated material are in excellent agreement. The key step, a [Cp*Ru(MeCN)3]PF6-catalyzed alkene-alkyne coupling, was used to form the 20-membered ring in the final step of the synthesis.

    View details for DOI 10.1021/ja049292k

    View details for Web of Science ID 000220957900005

    View details for PubMedID 15099060

  • An asymmetric synthesis of hamigeran B via a Pd asymmetric allylic alkylation for enantiodiscrimination JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pissot-Soldermann, C., Chen, I., Schroeder, G. M. 2004; 126 (14): 4480-4481

    Abstract

    A protocol for the asymmetric allylic alkylation of a five-membered ring ketone derivative that employs the lithium enolate in the presence of lithium alkoxides gave high yields and enantioselectivities. This product serves as a versatile intermediate as demonstrated in a convergent total synthesis of the antiviral agent hamigeran B. The sequence involves two unusual observations. In the intramolecular Heck reaction which establishes the complete ring sytem, the beta-H elimination step occurs both endocyclic (as expected) and exocyclic, the latter most surprising since it creates an exocylic tetrasubstituted double bond. In the catalytic hydrogenation, use of Pd/C gives complete selectivity for net delivery of hydrogen to the most hindered face of the substrate, whereas use of Ir black gives complete selectivity for delivery of hydrogen to the least hindered face. Such unusual behavior speaks to the unusual chemical properties associated with hamigeran B which may be relevant to its biological activity.

    View details for DOI 10.1021/ja0497025

    View details for Web of Science ID 000220752300010

    View details for PubMedID 15070341

  • Asymmetric catalysis: An enabling science PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Trost, B. M. 2004; 101 (15): 5348-5355

    Abstract

    Chirality of organic molecules plays an enormous role in areas ranging from medicine to material science, yet the synthesis of such entities in one enantiomeric form is one of the most difficult challenges. The advances being made stem from the convergence of a broader understanding of theory and how structure begets function, the developments in the interface between organic and inorganic chemistry and, most notably, the organic chemistry of the transition metals, and the continuing advancements in the tools to help define structure, especially in solution. General themes for designing catalysts to effect asymmetric induction are helping to make this strategy more useful, in general, with the resultant effect of a marked enhancement of synthetic efficiency.

    View details for DOI 10.1073/pnas.0306715101

    View details for Web of Science ID 000220861500010

    View details for PubMedID 14990801

    View details for PubMedCentralID PMC397384

  • Direct catalytic asymmetric aldol additions of methyl ynones. Spontaneous reversal in the sense of enantioinduction JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Fettes, A., Shireman, B. T. 2004; 126 (9): 2660-2661

    Abstract

    In this Communication, we report the direct, catalytic, asymmetric aldol addition of methyl ynones using our dinuclear zinc catalyst. A spontaneous reversal in the sense of enantioinduction was observed for these reactions; formation of the (S)-enantiomer is favored in the early stages (69% ee after 5 min), whereas the (R)-enantiomer is isolated as the major product after prolonged reaction times (97% ee after 22 h). It could be shown that this reversal in enantioselectivity is due to formation of a new catalytic species which incorporates the aldol product.

    View details for DOI 10.1021/ja038666r

    View details for Web of Science ID 000220038800003

    View details for PubMedID 14995157

  • New insights into the mechanism of molybdenum-catallyzed asymmetric alkylation 12th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-12) Krska, S. W., Hughes, D. L., Reamer, R. A., Mathre, D. J., Palucki, M., Yasuda, N., Sun, Y., Trost, B. M. WALTER DE GRUYTER GMBH. 2004: 625–33
  • 5H-oxazol-4-ones as building blocks for asymmetric synthesis of alpha-hydroxycarboxylic acid derivatives JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dogra, K., Franzini, M. 2004; 126 (7): 1944-1945

    Abstract

    5H-Alkyl-2-phenyl-oxazol-4-ones, a little-known heterocyclic ring system, are readily available via a microwave-assisted, sodium fluoride catalyst cyclization of mono-alpha-haloimides, which in turn are accessed by N-acylation of benzamides with alpha-bromo acid halides. Terminally substituted allyl systems serve as excellent substrates for Mo-catalyzed asymmetric allylic alkylation. The resultant products are formed with excellent ees involving a catalyst derived from N,N'-bis-picolinamide of trans-1,2-diaminocyclohexane and cycloheptatriene molybdenum tris(carbonyl). In addition to benzenoid, nonbenzenoid aromatic and vinyl substituents on the allyl carbonate moiety provide good to excellent regio- and diastereoselectivity as well as excellent enantioselectivity. Substituents on the heterocycle include methyl, n-butyl, allyl, isobutyl, isopropyl, and cyclohexyl. The presence of a double bond in the product allows them to be further modified via the chemistry of the double-bond, including metathesis. The products are hydrolyzed under basic conditions to provide alpha-hydroxyamides.

    View details for DOI 10.1021/ja031539a

    View details for Web of Science ID 000189096200011

    View details for PubMedID 14971921

  • A formal synthesis of (-)-mycalamide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Yang, H. B., Probst, G. D. 2004; 126 (1): 48-49

    Abstract

    Novel strategies are developed for an efficient formal synthesis of (-)-mycalamide A. The left-hand side (-)-7-benzoylpederic acid is synthesized from (2S,3S)-2,3-epoxybutane. The key features include a highly regioselective Ru-catalyzed alkene-alkyne coupling reaction and a novel way to control the challenging C(7) stereocenter. The right-hand side was synthesized from (R)-pantolactone. The complex trioxodecalin core is constructed with two Pd(0)-catalyzed O-pi-allyl cyclizations. The first one is chemoselective, while the second one is highly diastereoselective. Three additional steps would be required to complete a total synthesis of (-)-mycalamide A.

    View details for DOI 10.1021/ja038787r

    View details for Web of Science ID 000187945400024

    View details for PubMedID 14709053

  • Stereocontrolled total synthesis of (+)-streptazolin by a palladium-catalyzed reductive diyne cyclization ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Chung, C. K., Pinkerton, A. B. 2004; 43 (33): 4327-4329

    View details for DOI 10.1002/anie.200460058

    View details for Web of Science ID 000223603600015

    View details for PubMedID 15368383

  • Chemoselectivity of the ruthenium-catalyzed hydrative diyne cyclization: Total synthesis of (+)-cylindricine C, D, and E ORGANIC LETTERS Trost, B. M., Rudd, M. T. 2003; 5 (24): 4599-4602

    Abstract

    [reaction: see text] The chemoselectivity of the ruthenium-catalyzed hydrative diyne cylization is explored in an expeditious synthesis of the tricyclic alkaloids cylindricine C, D, and E.

    View details for DOI 10.1021/ol035752n

    View details for Web of Science ID 000186728600018

    View details for PubMedID 14627393

  • On the diastereoselectivity of Ru-catalyzed [5+2] cycloadditions ORGANIC LETTERS Trost, B. M., Shen, H. C., Schulz, T., Koradin, C., Schirok, H. 2003; 5 (22): 4149-4151

    Abstract

    [reaction: see text]. Ru-catalyzed cycloisomerization of cyclopropylenynes proceeds with good to high diastereoselectivities to form hexahydroazulenes.

    View details for DOI 10.1021/ol0355884

    View details for Web of Science ID 000186210800034

    View details for PubMedID 14572271

  • Total syntheses of furaquinocin A, B, and E JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Thiel, O. R., Tsui, H. C. 2003; 125 (43): 13155-13164

    Abstract

    A modular approach to the total synthesis of furaquinocins culminated in the total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck cyclization allows the enantio- and diastereoselective construction of dihydrobenzofuran 32. Introduction of a double unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the naphthoquinone with squaric acid based methodology leads to furaquinocin E. The use of differentially substituted squaric acid derivatives allows the synthesis of three analogues of furaquinocin E. The additional stereocenters in furaquinocin A and B can be introduced with a diastereoselective Sakurai allylation. The stereoselective elongation of the side chain is possible using cross metathesis or ring closing metathesis. The obtained late-stage intermediates were successfully transformed to furaquinocin A and B.

    View details for DOI 10.1021/ja0364118

    View details for Web of Science ID 000186123900044

    View details for PubMedID 14570490

  • Dynamic kinetic asymmetric cycloadditions of isocyanates to vinylaziridines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Fandrick, D. R. 2003; 125 (39): 11836-11837

    Abstract

    The first examples of the use of racemic vinylaziridines in a Pd-catalyzed dynamic kinetic asymmetric transformation have been examined. Optimization studies of the Pd-catalyzed addition of vinylaziridines to isocyanates revealed that the chiral ligand between trans-1,2-diaminocyclohexane and 2-diphenylphosphino-1-naphthoic acid is superior to that involving 2-diphenylphosphino benzoic acid. Surprisingly, high ee's required the use of an acid whose pKa was about 4.7 +/- 0.1 as a cocatalyst. Both acetic acid and hydroxybenzotriazole meet this requirement. Less electrophilic isocyanates (e.g., benzyl, p-methoxyphenyl) gave higher ee's than more electrophilic ones (phenyl or benzoyl). Both N-benzyl and N-arylaziridines react well to give good yields and ee's, whereas N-tosylaziridines gave lower ee's. A 1,1-disubstituted aziridine led to the formation of a tertiary C-N bond with ee's comparable to the formation of the secondary C-N bond. The products were easily reduced almost quantitatively to the sensitive imidazolidines which can be readily hydrolyzed to the vicinal diamines. The reactivity pattern is consistent with a Curtin-Hammett situation wherein the enantiodiscriminating event is the cyclization of a rapidly equilibrating dynamic pi-allyl palladium intermediate.

    View details for DOI 10.1021/ja037450m

    View details for Web of Science ID 000185578500032

    View details for PubMedID 14505403

  • A mechanistic dichotomy in ruthenium-catalyzed propargyl alcohol reactivity: A novel hydrative diyne cyclization JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rudd, M. T. 2003; 125 (38): 11516-11517

    Abstract

    The cycloisomerization of diyne-ols catalyzed by [CpRu(CH3CN)3]PF6 to 2-vinyl-1-acylcycloalkenes proceeds via a ruthenacyclopentadiene involving initial ionization of the tertiary or secondary alcohol, followed by readdition. In the case of primary alcohols, a competing pathway wherein water first adds would appear to occur. The feasibility of this proposed minor pathway was tested in the reaction of diynes in the presence of water. Quite excitingly, cyclization comcommittant with addition of water to form 1-acylcycloalkenes occurs. This proves to be general process to form five- and six-membered rings. Interestingly, hydrative cyclization of Z-5-decen-2,8-diyne to 1-acetyl-2-ethyl-cyclohexa-1,4-diene occurs without isomerization of the double bonds. Furthermore, the epoxide of the same substrate cyclizes without opening of the strained epoxide. Unsymmetrically substituted diynes cyclize with remarkable chemoselectivity wherein water attacks the less hindered alkynes. beta-branching of any kind gives only a single product. Remarkably, even competing methyl versus ethyl still effects a 2.5:1 selectivity in favoring water addition to the methyl-bearing alkyne. Alcohols can replace water and provide enol ethers. Strong mechanistic evidence suggests two reaction manifolds indeed operate, depending upon the presence of propargyl alcohols and the degree of substitution on the hydroxyl-bearing carbon.

    View details for DOI 10.1021/ja036410f

    View details for Web of Science ID 000185711100031

    View details for PubMedID 13129352

  • Asymmetric synthesis of oxygen heterocycles via Pd-catalyzed dynamic kinetic asymmetric transformations: Application to nucleosides CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Brown, B. S., McEachern, E. J., Kuhn, O. 2003; 9 (18): 4442-4451

    Abstract

    Racemic butadiene and isoprene monoepoxide react with unsaturated alcohols in the presence of a chiral palladium catalyst and a boron co-catalyst to give 3-alkoxy-4-hydroxy-1-butene and 3-alkoxy-4-hydroxy-3-methyl-1-butene, respectively, with excellent regio- and enantioselectivity in a dynamic kinetic asymmetric transformation whereby both enantiomers of the starting epoxides provide the same enantiomeric product. In the case of 2-phenylbutadiene monoepoxide, easily available from phenacyl chloride and vinylmagnesium bromide, the reaction proceeds by kinetic resolution. A model to rationalize the result is presented. The bis-olefin products are ideal substrates for the Ru catalyzed ring closing metathesis. In this way, five-, six-, and seven-membered oxygen heterocycles are readily available enantiomerically pure. The value of this very simple two step process is demonstrated by the use of the five-membered ring heterocycles to form unnatural and unusual nucleosides that cannot be easily accessed by other means. The sequence involves a Ru catalyzed isomerization of the initial 2,5-dihydrofuran to a 2,3-dihydrofuran followed by a selenium promoted addition of a pyrimidine or purine base. One advantage of this strategy is the easy access to either enantiomeric series, both of which have important biological applications.

    View details for DOI 10.1002/chem.200304949

    View details for Web of Science ID 000185583400019

    View details for PubMedID 14502631

  • Unusual effects in the Pd-catalyzed asymmetric allylic alkylations: Synthesis of chiral chromans JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Shen, H. C., Dong, L., Surivet, J. P. 2003; 125 (31): 9276-9277

    Abstract

    An examination of earlier reports of poor-to-modest results using Pd-catalyzed asymmetric allylic alkylations (AAA) to effect cyclization to form tetrasubstituted carbons reveals several novel factors that can influence this class of reactions. Thus, carboxylate has a major effect on such cyclizations wherein the ee increases from 14% ee favoring the S with no carboxylate to 84% ee favoring the R enantiomer in the presence of 1 equiv of carboxylate. Changing the double bond geometry from E to Z further increases the ee to 97%. Furthermore, the chiral catalyst that forms the R enantiomer with the E-alkene forms the S enantiomer with the Z alkene. In contrast to trisubstituted alkene substrates, disubstituted ones show a decrease in ee in going from the E to Z alkenes. The role of carboxylate appears to be a ligand to Pd during the catalytic cycle, a previously unsuspected phenomenon since such reactions are generally believed to involve pi-allylpalladium cationic complexes. The dependence upon alkene geometry helps define the nature of the chiral pocket which better accommodates a Z alkene compared to an E alkene. The results are compatible with the enantiodiscriminating step being ionization which occurs by coordination of the palladium to one of the two prochiral faces of the double bond. A synthesis of (+)-clusifoliol, a constituent of a folk medicine for treatment of malignant tumors, which also assigns the absolute configuration, illustrates the utility of the method.

    View details for DOI 10.1021/ja036052g

    View details for Web of Science ID 000184515300019

    View details for PubMedID 12889940

  • Asymmetric transition-metal-catalyzed allylic alkylations: Applications in total synthesis CHEMICAL REVIEWS Trost, B. M., Crawley, M. L. 2003; 103 (8): 2921-2943

    View details for DOI 10.1021/cr020027w

    View details for Web of Science ID 000184821500008

    View details for PubMedID 12914486

  • Migratory hydroamination: A facile enantioselective synthesis of benzomorphans JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Tang, W. P. 2003; 125 (29): 8744-8745

    Abstract

    We describe a highly efficient, general strategy for the enantioselective synthesis of benzomorphans (45-46% overall yield from commercially available material). The new synthesis demonstrates the effectiveness of an unprecedented diastereoselective cycloisomerization via migratory hydroamination and the power of palladium-catalyzed asymmetric allylic alkylation (AAA) of simple ketone enolates in the context of complex synthesis. The strategy outlined here for the enantioselective synthesis of three contiguous stereogenic centers and the novel cycloisomerization should have many applications in alkaloid synthesis.

    View details for DOI 10.1021/ja0360539

    View details for Web of Science ID 000184243000026

    View details for PubMedID 12862467

  • A Rh(I)-catalyzed cycloisomerization of homo- and bis-homopropargylic alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rhee, Y. H. 2003; 125 (25): 7482-7483

    Abstract

    The ability to form rhodium-vinylidene complexes in situ from terminal alkynes has led to the development of a catalytic process, the cycloisomerization of homopropargylic and bis-homopropargylic alcohols to dihydrofurans and dihydropyrans. Among the transition metals that perform similar reactions, rhodium catalysts demonstrate the best chemoselectivity and turnover numbers to date. Both secondary and tertiary alcohols participate equally well. The presence of proparylic oxygen and nitrogen functionality, which potentially can be induced to ionize via formation of allenylidene metal complexes, is compatible with this catalyst. The formation of a 5-amino-dihydropyran which is not compatible with some of the previous catalysts proceeds in good yield with the rhodium catalysts. A substrate bearing a benzylic hydroxyl group adjacent to an electron-rich aromatic ring also participates without complications of ionization. The method provides access to useful aminosugars. A mechanism to account for the different selectivity of this catalyst as compared to others is proposed.

    View details for DOI 10.1021/ja0344258

    View details for Web of Science ID 000183646400001

    View details for PubMedID 12812465

  • Ruthenium-catalyzed vinylsilane synthesis and cross-coupling as a selective awroach to alkenes: Benzyldimethylsilyl as a robust vinylmetal functionality ORGANIC LETTERS Trost, B. M., Machacek, M. R., Ball, Z. T. 2003; 5 (11): 1895-1898

    Abstract

    [reaction: see text] Ruthenium-catalyzed alkyne hydrosilylation or silyl-alkyne Alder ene reactions provide entry into benzyldimethylsilyl (BDMS)-substituted alkenes. The BDMS-vinylsilanes are further elaborated through mild palladium-catalyzed cross coupling and show significant stability to intervening synthetic operations, including silyl ether deprotection.

    View details for DOI 10.1021/ol034463w

    View details for Web of Science ID 000183129000023

    View details for PubMedID 12762680

  • Pd-catalyzed asymmetric allylic alkylation. A short route to the cyclopentyl core of viridenomycin ORGANIC LETTERS Trost, B. M., Jiang, C. H. 2003; 5 (9): 1563-1565

    Abstract

    A palladium-catalyzed asymmetric allylic alkylation effects a dynamic kinetic asymmetric transformation of racemic isoprene monoepoxide and a surrogate for Nazarov's reagent in which a quaternary center is created with exellent ee. The resultant adduct allows easy access to a substrate for ring-closing metathesis to form a cyclopentenone and sets the stage for an 11-step synthesis of the cyclopentyl core of the antibiotic antitumor agent viridenomycin. [reaction: see text]

    View details for DOI 10.1021/ol0343515

    View details for Web of Science ID 000182498500045

    View details for PubMedID 12713324

  • Ruthenium-catalyzed alkyne-propargyl alcohol addition. An asymmetric total synthesis of (+)-alpha-kainic acid ORGANIC LETTERS Trost, B. M., Rudd, M. T. 2003; 5 (9): 1467-1470

    Abstract

    A novel route to the neuroexcitatory amino acid, kainic acid, is developed. The key concept derives from a ruthenium-catalyzed cycloisomerization of a tethered alkyne-propargyl alcohol to form a cyclic 2-vinyl-1-acyl compound. A single stereocenter introduced by an asymmetric reduction of a ketone sets the stage for all the other stereocenters. A novel 1,6-addition of silyl cuprate serves to install a hydroxyl group at the diene termines. [reaction: see text]

    View details for DOI 10.1021/ol034241y

    View details for Web of Science ID 000182498500021

    View details for PubMedID 12713300

  • Palladium-catalyzed asymmetric addition of pronucleophiles to allenes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Jakel, C., Plietker, B. 2003; 125 (15): 4438-4439

    Abstract

    Simple additions are the most atom economic way to effect alkylations. The ability to effect the hydrocarbonation of allenes asymmetrically then becomes a highly efficient alkylation protocol. The first example of such a protocol involves the ability of a palladium(0) catalyst derived from palladium trifluoroacetate dimer and the bis-2-diphenylphosphinobenzamide of trans-1,2-diamininocyclohexane to catalyze additions to benzyloxyalkene. Various substituted Meldrum's acids including hydroxy Meldrum's acid react well in the presence of 1 mol % trifluoroacetic acid to give one regioisomer with ee's ranging from 82 to 99%. Switching to azlactones to access unusual quarternary amino acids requires somewhat more basic conditions. Thus, use of 2 mol % potassium alpha-butoxide and 20 mol % hippuric acid leads to a smooth reaction to produce a simple regiosomer. This nucleophile raises the question of facial selectivity with respect to both the nucleophile and the electrophile. Excellent diastereoselectivity (dr 13-20:1) and enantioselectivity (85-94% ee) are obtained. Thus, a new approach for asymmetric allylic alkylations of carbon pronucleophiles by simple additions provides a very efficient, more atom economic strategy for asymmetric C-C bond formation.

    View details for DOI 10.1021/ja029190z

    View details for Web of Science ID 000182137800019

    View details for PubMedID 12683811

  • Atom economy. Palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a net C-H insertion JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D., Greenman, K. 2003; 125 (15): 4518-4526

    Abstract

    A strategy to achieve ortho substitution of phenols initiated by an ortho-palladation to create coumarins was examined. Indeed, treatment of alkynoates with electron-rich phenols in the presence of a palladium catalyst and an acid does generate coumarins. The scope of the reaction with respect to the phenol and the alkynoates is defined. With unsymmetrical aromatic substrates, generally good regioselectivity that reflects the HOMO coefficients can be observed. In the course of these studies, numerous important naturally occurring coumarins have been synthesized, including fraxinol methyl ether, ayapin, herniarin, xanthoxyletin, and alloxanthoxyletin. The fact that a Pd(0) is the precatalyst rather than a Pd(+2) species and that an acid that reduces Pd(+2) salts, formic acid, functions better than other carboxylic acids raises doubts about the initial working hypothesis. A novel mechanism involving a palladium phenoxide formed from a hydridopalladium carboxylate and phenol is invoked to rationalize the results.

    View details for DOI 10.1021/ja0286573

    View details for Web of Science ID 000182137800030

    View details for PubMedID 12683822

  • Palladium catalyzed kinetic and dynamic kinetic asymmetric transformations of gamma-acyloxybutenolides. Enantioselective total synthesis of (+)-aflatoxin B-1 and B-2a JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 2003; 125 (10): 3090-3100

    Abstract

    The reaction of gamma-tert-butoxycarbonyloxy-2-butenolide with phenol nucleophiles in the presence of a Pd(0) complex with chiral ligands may be performed under conditions that favor either a kinetic resolution or a kinetic asymmetric transformation (KAT) or dynamic kinetic asymmetric transformation (DYKAT). Performing the reaction at high concentration (0.5 M) in the presence of a carbonate base favors the former, i.e., KAT; whereas, running the reaction at 0.1M in the presence of tetra-n-butylammonium chloride favors the DYKAT process. Syntheses of aflatoxin B(1) and B(2a) employs the DYKAT to introduce the stereochemistry. Starting with Pechmann condensation of the monomethyl ether of phloroglucinol, the requisite phenol nucleophile is constructed in two steps. The DYKAT proceeds with > 95% ee. A reductive Heck cyclization followed by a lanthanide catalyzed intramolecular acylation completes the synthesis of the pentacyclic nucleus in 3 steps. Reduction of the lactone provides aflatoxin B(2a) and its dehydration product B(1). This synthetic strategy creates an asymmetric synthesis of the former in only 7 steps and the latter in 9 steps. Thus, the ultimate synthetic sequence involves 3 + 5 --> 39 --> 40 --> 42 --> 43 --> 46 --> 47 --> 48 (aflatoxin B(2a)) --> 49 (aflatoxin B(1)).

    View details for DOI 10.1021/ja020988s

    View details for Web of Science ID 000181409500056

    View details for PubMedID 12617676

  • Desymmetrization of meso 1,3-and 1,4-diols with a dinuclear zinc asymmetric catalyst JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Mino, T. 2003; 125 (9): 2410-2411

    Abstract

    A dinuclear asymmetric zinc catalyst generated by mixing a 2:1 ratio of diethylzinc and 2,6-bis[5-2-diarylhydroxy methyl-1-pyrrolidinyl]-4-methylphenol has been contrasted with enzymes for the desymmetrization of some meso diols. The best ligand has a p-biphenylyl group as the aromatic substituent defining the chiral space. A series of 2-substituted propanediols were examined. The best acyl transfer agent proved to be vinyl benzoate. Diacylation normally did not occur. The phenyl substituted substrate gave 91-95% ee which compares favorably with the best ee of 92% reported for an enzymatic desymmetrization. The methyl substituted substrate gave significantly better results with the dinuclear zinc catalyst (89% yield, 82% ee) as compared to the best enzymatic esterification (70% yield, 60% ee). One case of a 1,4-diol, cis-1,2-bis(hydroxymethyl) cyclohexane, also gave much better results with the dinuclear zinc catalysts (93% yield, 91% ee) as compared to the reported enzymatic process (44% yield, 7% ee). A model to rationalize the results is presented.

    View details for DOI 10.1021/ja029708z

    View details for Web of Science ID 000181235800023

    View details for PubMedID 12603126

  • A direct catalytic asymmetric Mannich-type reaction to syn-amino alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Terrell, L. R. 2003; 125 (2): 338-339

    Abstract

    The Mannich reaction is one of the most widely utilized chemical transformations for the construction of nitrogen-containing compounds. With the increasing occurrence of nitrogen in drugs and natural products, highly asymmetric variants of the Mannich reaction are desirable. In this communication, we report the application of our dinuclear zinc catalyst to a highly asymmetric Mannich-type reaction to generate syn 1,2-amino alcohols.

    View details for DOI 10.1021/ja028782e

    View details for Web of Science ID 000180311800016

    View details for PubMedID 12517138

  • Intramolecular endo-dig hydrosilylation catalyzed by ruthenium: Evidence for a new mechanistic pathway JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T. 2003; 125 (1): 30-31

    Abstract

    The ruthenium catalyst [Cp*Ru(MeCN)3]PF6 effects a novel intramolecular hydrosilylation of homo- and bis-homopropargylic alcohols, producing products of unique regioselectivity under very mild conditions with excellent selectivity. The reaction is compatible with a wide range of functional groups and tolerates substantial steric bulk. In addition to producing valuable synthetic intermediates thus far obtainable only in circuitous fashion, the results imply the necessity for a reexamination of the mechanism surrounding trans-hydrosilylation reactions, at least for ruthenium catalysts. At the very least, a simple cis addition/isomerization mechanism almost certainly cannot be active in this case. A silicon-ruthenium transposition could potentially provide a rationalization. However, the evidence for any products of syn addition with nonhydrido ruthenium catalysts is very scarce. Alternatively, a direct trans addition to orthogonal p-systems is also a possibility.

    View details for DOI 10.1021/ja028966h

    View details for Web of Science ID 000180227400012

    View details for PubMedID 12515496

  • Regioselective hydrosilylation of propargylic alcohols: An aldol surrogate ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Ball, Z. T., Joge, T. 2003; 42 (29): 3415-3418

    View details for DOI 10.1002/anie.200351587

    View details for Web of Science ID 000184548700020

    View details for PubMedID 12888974

  • Vanadium-catalyzed anti-selective additions of allenols to imines ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Jonasson, C. 2003; 42 (18): 2063-2066

    View details for DOI 10.1002/anie.200350890

    View details for Web of Science ID 000183047100017

    View details for PubMedID 12746824

  • An enantioselective biomimetic total synthesis of (-)-siccanin ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Shen, H. C., Surivet, J. P. 2003; 42 (33): 3943-3947

    View details for DOI 10.1002/anie.200351868

    View details for Web of Science ID 000185098200019

    View details for PubMedID 12949876

  • Palladium-catalyzed DYKAT of vinyl epoxides: Enantioselective total synthesis and assignment of the configuration of (+)-broussonetine G ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Horne, D. B., Woltering, M. J. 2003; 42 (48): 5987-5990

    View details for DOI 10.1002/anie.200352857

    View details for Web of Science ID 000187570400015

    View details for PubMedID 14679550

  • Enantioselective synthesis of (-)-codeine and (-)-morphine JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Tang, W. P. 2002; 124 (49): 14542-14543

    Abstract

    A new synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges employing a Pd-catalyzed asymmetric allylic alkylation to set the stereochemistry. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate, the latter available from glutaraldehyde and the Emmons-Wadsworth-Horner phosphate reagent. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine is formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.

    View details for DOI 10.1021/ja0283394

    View details for Web of Science ID 000179661000018

    View details for PubMedID 12465957

  • Utilization of molybdenum- and palladium-catalyzed dynamic kinetic asymmetric transformations for the preparation of tertiary and quaternary stereogenic centers: A concise synthesis of tipranavir JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Andersen, N. G. 2002; 124 (48): 14320-14321

    Abstract

    Tipranavir, an important antiviral agent in clinical development for the treatment of HIV, is synthesized in 15 linear steps from readily available starting materials in 25% overall yield by utilizing Pd- and Mo-catalyzed DYKAT reactions to control the quaternary and tertiary stereogenic centers, respectively.

    View details for DOI 10.1021/ja028497v

    View details for Web of Science ID 000179510800020

    View details for PubMedID 12452702

  • The unusual role of CO transfer in molybdenum-catalyzed asymmetric alkylations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Krska, S. W., Hughes, D. L., Reamer, R. A., Mathre, D. J., Sun, Y., Trost, B. M. 2002; 124 (43): 12656-12657

    Abstract

    Spectroscopic and crystallographic studies were undertaken to gain insight into the mechanism of the highly regio- and enantioselective allylic aklylation reaction catalyzed by molybdenum. The chiral ligand (L*) consisting of the mixed benzamide/picolinamide of (S,S,)-trans-1,2-diaminocyclohexane reacts with a typical Mo precatalyst, (norbornadiene)Mo(CO)4, to give a neutral complex L*Mo(CO)4 in which the ligand binds to the metal in a bidentate fashion through the pyridine and adjacent amide group. Reaction of this complex with the methyl carbonate of cinnamyl alcohol gives the corresponding pi-allyl complex L*(CO)2Mo(eta3-CH2=CH-CHPh). NMR and X-ray crystallographic characterization of this complex reveal the ligand binds in a facially capping tridentate fashion via the pyridine nitrogen, the nitrogen of the adjacent amide group, which has now been deprotonated, and the carbonyl oxygen of the remote amide. Surprisingly, the face of the allyl group open to attack with nucleophiles is that which would lead to the sense of stereochemistry opposite to that which is observed in catalytic reactions. Furthermore, the allyl complex in its isolated form is unreactive toward sodium dimethyl malonate. However, in the presence of a source of carbon monoxide (either Mo(CO)6 or gaseous CO), the allyl complex reacts with malonate to give the typically observed branched alkylated product in high yield and enantiomeric excess. The metal-containing product of this reaction is the molybdate complex [L*Mo(CO)4]-Na+. Reaction of the molybdate complex with linear or branched allylic carbonates regenerates the allyl complex, thus closing the catalytic cycle. Both the allyl complex and the molybdate complex are the only metal-containing species observed by NMR in typical catalytic reactions and thus appear to be catalyst resting states. Turnover of the catalytic cycle therefore involves shuttling of carbon monoxide between the two catalyst resting states. Coordination of CO appears to be necessary to activate the allyl complex toward nucleophilic attack, in effect stabilizing the molybdenum fragment as a leaving group.

    View details for DOI 10.1021/ja028035h

    View details for Web of Science ID 000178792400011

    View details for PubMedID 12392401

  • Ruthenium-catalyzed alkene-alkyne coupling: Synthesis of the proposed structure of amphidinolide A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Chisholm, J. D., Wrobleski, S. T., Jung, M. 2002; 124 (42): 12420-12421

    Abstract

    The ruthenium-catalyzed alkene-alkyne coupling provides a powerful method for the synthesis of 1,4 dienes and a way to simplify synthetic strategy. The latter potential is explored in the context of a synthesis of the assigned structure of amphidinolide A, which also raises the question of the applicability of this reaction for macrocyclizations. Employing this reaction allows simplification of the target to three subunits corresponding to C-1 to C-6, C-7 to C-15, and C-16 to C-25. The C-7 to C-15 subunit involves introduction of chirality by an asymmetric dihydroxylation. The route to the C-16 to C-25 subunit introduces chirality by a Pd-catalyzed asymmetric allylic alkylation and an asymmetric epoxidation. Assembly of the three subunits employs the Ru-catalyzed addition inter- and intramolecularly. The synthesis culminated in the formation of the assigned structure and is identical to the synthetic samples prepared independently by two completely different routes. As noted by the other two groups, this structure appears to be a diastereomer of the natural product. Because this synthesis introduces all of the stereochemistry of the subunits by catalytic asymmetric processes, either enantiomer as well as diastereomers can be readily accessed to define the correct structure. Notably, the Ru-catalyzed macrocyclization to this macrolide proceeded in better yields than either a Pd-catalyzed cross-coupling or a Ru-catalyzed metathesis, macrocylization methods for the other two total synthesis.

    View details for DOI 10.1021/ja027883

    View details for Web of Science ID 000178672900014

    View details for PubMedID 12381177

  • An acid-catalyzed macrolactonization protocol ORGANIC LETTERS Trost, B. M., Chisholm, J. D. 2002; 4 (21): 3743-3745

    Abstract

    [reaction: see text] An efficient macrolactonization protocol devoid of any base was developed derived from the use of vinyl esters in transesterification. Subjecting a hydroxy acid and ethoxyacetylene to 2 mol % [RuCl(2)(p-cymene)](2) in toluene followed by addition of camphorsulfonic acid or inverse addition provided macrolactones in good yields.

    View details for DOI 10.1021/ol026726c

    View details for Web of Science ID 000178522700049

    View details for PubMedID 12375933

  • Stereocontrolled synthesis of (+)-boronolide ORGANIC LETTERS Trost, B. M., Yeh, V. S. 2002; 4 (20): 3513-3516

    Abstract

    Boronolide was synthesized stereoselectively from hydroxyacetylfuran 5 and valeraldehyde 6 using a novel dizinc aldol catalyst. Ring closing metathesis provides the lactone ring. The synthesis requires 12 steps and proceeds in 26% overall yield. [reaction: see text]

    View details for DOI 10.1021/ol026665i

    View details for Web of Science ID 000178327500045

    View details for PubMedID 12323057

  • Intramolecular palladium-catalyzed allylic alkylation: Enantio- and diastereoselective synthesis of [2.2.2] bicycles ORGANIC LETTERS Trost, B. M., Sacchi, K. L., Schroeder, G. M., Asakawa, N. 2002; 4 (20): 3427-3430

    Abstract

    Pd-catalyzed asymmetric allylic alkylation provides both enantio- and diastereoselectivity in formation of bicyclo [2.2.2] octan-2,3-diones and quinuclidin-2-ones, the latter potential precursors to quinine alkaloids. [reaction: see text]

    View details for DOI 10.1021/ol0265766

    View details for Web of Science ID 000178327500023

    View details for PubMedID 12323035

  • DYKAT of Baylis-Hillman adducts: Concise total synthesis of furaquinocin E JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Thiel, O. R., Tsui, H. C. 2002; 124 (39): 11616-11617

    Abstract

    Baylis-Hillman adducts are easily accessible building blocks; the lack of asymmetric versions of the Baylis-Hillman reaction has however precluded their widespread use in asymmetric synthesis. A Pd-catalyzed DYKAT on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck reaction, allows the enantio- and diastereoselective construction of dihydrobenzofurans in a very efficient manner. These synthons represent the core structure of the furaquinocins. Introduction of different side chains and use of different squaric acid derivatives for the construction of the naphthoquinone allow the flexible synthesis of this class of natural products. This new approach is successfully applied to the synthesis of furaquinocin E and an analogue.

    View details for DOI 10.1021/ja0277834

    View details for Web of Science ID 000178317100028

    View details for PubMedID 12296725

  • Callipeltoside A: Total synthesis, assignment of the absolute and relative configuration, and evaluation of synthetic analogues JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Gunzner, J. L., Dirat, O., Rhee, Y. H. 2002; 124 (35): 10396-10415

    Abstract

    The total synthesis of the novel antitumor agent callipeltoside A, as well as several analogues, is accomplished and allows assignment of the stereochemistry not previously established. A convergent strategy is employed wherein the target is dissected into three units-the core macrolactone, the sugar callipeltose, and a cyclopropyl bearing chain. The strategy for the synthesis of the macrolactone derives from employment of diastereoselective aldol reactions that emanate from an 11 carbon piece. The stereochemistry of the latter derives from the chiral pool and two asymmetric reactions-a ketone reduction using CBS-oxazaborolidine and a Pd catalyzed asymmetric allylic alkylation (AAA). The novelty of the latter protocol is its control of regioselectivity as well as absolute configuration. The trisubstituted olefin is generated using an alkene-alkyne coupling to create a trisubustituted olefin with complete control of geometry. The excellent chemo- and regioselectivity highlights the synthetic potential of this new ruthenium catalyzed process. The macrolactonization employs in situ formation of an acylketene generated by the thermolysis of a m-dioxolenone. Two strategies evolved for attachment of the side chain-one based upon olefination and a second upon olefin metathesis. The higher efficiency of the latter makes it the method of choice. A novel one pot olefin metathesis-Takai olefination protocol that should be broadly applicable is developed. The sugar is attached by a glycosylation by employing the O-trichloroacetimidate. This route provided both C-13 epimers of the macrolactone by using either enantiomeric ligand in the Pd AAA reaction. It also provided both trans-chlorocyclopropane diastereomers of callipeltoside A which allows the C-20 and C-21 configuration to be established as S and R, respectively. The convergent nature of the synthesis in which the largest piece, the macrolatone, require only 16 linear steps imparts utility to this strategy for the establishment of the structure-activity relationship. Initial biological testing demonstrates the irrelevance of the chloro substituent and the necessity of the sugar.

    View details for DOI 10.1021/ja0205232

    View details for Web of Science ID 000177881300037

    View details for PubMedID 12197742

  • On inventing reactions for atom economy ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M. 2002; 35 (9): 695-705

    Abstract

    An important first step in making organic reactions more environmentally benign by design requires processes that are, to a first approximation, simple additions with anything else needed only catalytically. Since so few of the existing reactions are additions, synthesis of complex molecules requires the development of new atom-economic methodology. The prospect for such developments is probed in the context of ruthenium-catalyzed reactions. Using mechanistic reasoning, over 20 new processes of varying complexity have been designed and implemented. While some involved oxidation-reduction processes, most involved C-C bond-forming reactions.

    View details for DOI 10.1021/ar010068z

    View details for Web of Science ID 000178085700003

    View details for PubMedID 12234199

  • Dinuclear Zn catalyst for the asymmetric Nitro-Aldol (Henry) reaction. Trost, B. M., Yeh, V. S. AMER CHEMICAL SOC. 2002: U198–U198
  • 4-Aryloxybutenolides as "chiral aldehyde" equivalents: An efficient enantioselective synthesis of (+)-brefeldin A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Crawley, M. L. 2002; 124 (32): 9328-9329

    Abstract

    4-(2'-Naphthoxy)-2-butenolide, readily available with high enantiopurity by a dynamic kinetic asymmetric transformation (DYKAT) of racemic 4-acyloxybutenolides (available in two steps from furfural), serves as an excellent chiral building block where the naphthoxy group strongly directs the stereochemistry of cycloadditions to the double bond. Notably, the cycloadditions of trimethylenemethanepalladium intermediates which do not exhibit good diastereoselectivity in additions to acceptors that possess many common and important chiral auxiliaries undergo cycloadditions with excellent regio- and stereocontrol. The utility of this process set the stage for an efficient new synthesis of (+)-brefeldin A, a compound of growing pharmacological significance. This synthesis also highlights the Pd-catalyzed DYKAT of crotyl carbonate to create the remote stereocenter. A new two-step method to convert aldehydes to delta-hydroxy-E-alpha,beta-enoates is also outlined.

    View details for DOI 10.1021/ja026438b

    View details for Web of Science ID 000177358600003

    View details for PubMedID 12167000

  • Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine ORGANIC LETTERS Trost, B. M., Yeh, V. S., Ito, H., Bremeyer, N. 2002; 4 (16): 2621-2623

    Abstract

    [reaction: see text] Syntheses of variously modified ligands for the dinuclear zinc catalysts for the asymmetric aldol and nitroaldol (Henry) reactions are reported. Catalytic enantioselective nitroaldol reactions promoted by these modified ligands led to efficient syntheses of the beta-receptor agonists (-)-denopamine and (-)-arbutamine.

    View details for DOI 10.1021/ol020077n

    View details for Web of Science ID 000177319200003

    View details for PubMedID 12153193

  • A chemoselective reduction of alkynes to (E)-alkenes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T., Joge, T. 2002; 124 (27): 7922-7923

    Abstract

    The trans reduction of all types of alkynes to give (E)-olefins is achieved through a two-stage trans hydrosilylation and protodesilylation. Reaction of an alkyne and a silane with the ruthenium catalyst [Cp*Ru(MeCN)3]PF6 results in clean hydrosilylation to give only the (Z)-trans addition product at ambient temperature with catalyst loadings of 1-5 mol %. The crude vinylsilane products are then protodesilylated by the action of cuprous iodide and TBAF at rt-35 degrees C. The reaction is compatible with many sensitive functional groups and provides a general trans-alkyne reduction not possible by other means.

    View details for DOI 10.1021/ja0264571

    View details for Web of Science ID 000176612400022

    View details for PubMedID 12095335

  • Formation of vinyl halides via a ruthenium-catalyzed three-component coupling JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B. 2002; 124 (25): 7376-7389

    Abstract

    The ruthenium-catalyzed three-component coupling of an alkyne, an enone, and halide ion to form E- or Z-vinyl halides has been investigated. Through systematic optimization experiments, the conditions effecting the olefin selectivity were examined. In general, more polar solvents such as DMF favored the formation of the E-isomer, and less polar solvents such as acetone favored formation of the Z-isomer. The optimized conditions for the formation of E-vinyl chlorides were found to be the use of cyclopentadienyl ruthenium (II) cyclooctadiene chloride, stannic chloride pentahydrate as a cocatalyst, and for a chloride source, either ammonium chloride in DMF/water mixtures or tetramethylammonium chloride in DMF. A range of several other ruthenium (II) catalysts was also shown to be effective. A wide variety of vinyl chlorides could be formed under these conditions. Substrates with tethered alcohols or ketones either five or six carbons from the alkyne portion gave instead diketone or cyclohexenone products. For formation of vinyl bromides, a catalyst system involving the use of cyclopentadienylruthenium (II) tris(acetonitrile) hexafluorophosphate with stannic bromide as a cocatalyst was found to be most effective. The use of ammonium bromide in DMF/acetone mixtures was optimal for the synthesis of E-vinyl bromides, and the use of lithium bromide in acetone was optimal for formation of the corresponding Z-isomer. Under either set of conditions, a wide range of vinyl bromides could be formed. When alkynes with propargylic substituents are used, enhanced selectivity for formation of the Z-isomer is observed. When aryl acetylenes are used as the coupling partners, complete selectivity for the Z-isomer is obtained. A mechanism involving a cis or trans halometalation is invoked to explain formation of the observed products. The vinyl halides have been shown to be precursors to alpha-hydroxy ketones and cyclopentenones, and as coupling partners in Suzuki-type reactions.

    View details for DOI 10.1021/ja011426w

    View details for Web of Science ID 000176338400029

    View details for PubMedID 12071746

  • Synthesis of novel quaternary amino acids using molybdenum-catalyzed asymmetric allylic alkylation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Dogra, K. 2002; 124 (25): 7256-7257

    Abstract

    The Mo-catalyzed asymmetric allylic alkylation using azlactones provides extraordinary levels of selectivity. Thus, a wide range of cinnamyl-type substrates react with 2-methyl and 2-benzyl azlactones to give only the product resulting from attack at the more substituted carbon. Using other alkyl substituents such as 2-methylthioethyl, isobutyl, allyl, and isopropyl provides products that still retain excellent regioselectivity but small quantities of the linear product are also observed. In all cases, excellent diastereo- and enantioselectivity of the branched alkylated product are observed. This new asymmetric reaction provides ready access to unusual quarternary amino acids, important building blocks for biological applications. The reactions complements the Pd AAA wherein the cinnamyl substrate leads to only the product of attack at the primary terminus of the allyl moiety.

    View details for DOI 10.1021/ja020290e

    View details for Web of Science ID 000176338400002

    View details for PubMedID 12071719

  • Chemo-, regio-, and enantioselective Pd-catalyzed allylic alkylation of indolocarbazole pro-aglycons ORGANIC LETTERS Trost, B. M., Krische, M. J., Berl, V., Grenzer, E. M. 2002; 4 (12): 2005-2008

    Abstract

    [reaction: see text] Monosubstituted isomerically pure indolopyrrolocarbazole precursors have been prepared via palladium-catalyzed asymmetric allylic alkylation methodology, employing both achiral cyclopentenyl electrophiles and chiral glycal derivatives. Chemoselective allylation of (bis)indole lactam pro-aglycon 3 allows access to N-distally substituted indolopyrrolocarbazole derivatives; glyoxamide precursor 14 provides entry into N-proximally substituted derivatives.

    View details for DOI 10.1021/ol020046s

    View details for Web of Science ID 000176185300007

    View details for PubMedID 12049503

  • A convenient synthetic route to [CpRu(CH3CN)(3)]PF6 ORGANOMETALLICS Trost, B. M., Older, C. M. 2002; 21 (12): 2544-2546

    View details for DOI 10.1021/om020143p

    View details for Web of Science ID 000176129500032

  • A synthesis of trisubstituted alkenes by a Ru-catalyzed addition CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Shen, H. C., Pinkerton, A. B. 2002; 8 (10): 2341-2349

    Abstract

    Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.

    View details for Web of Science ID 000175771300016

    View details for PubMedID 12012418

  • Mechanistic dichotomy in CpRu(CH3CN)(3)PF6 catalyzed enyne cycloisomerizations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 2002; 124 (18): 5025-5036

    Abstract

    Enynes are easily accessible building blocks as a result of the rich chemistry of alkynes and thus represent attractive substrates for ring formation. A ruthenium catalyst for cycloisomerization effects such reaction of 1,6- and 1,7-enynes typically at room temperature in acetone or DMF under neutral conditions. The reaction is effective for forming five- and six-membered rings of widely divergent structure. The alkyne may bear both election-donating and election-withdrawing substituents. The alkene may be di- or trisubstituted. Introduction of a quaternary center at the propargylic position of an ynoate, however, completely changes the nature of the reaction. In the case of a 1,6-enynoate, a seven-membered ring forms in excellent yield under equally mild conditions. Evidence is presented to indicate a complete change in mechanism. In the former case, the reaction involves the intermediacy of a ruthenacyclopentene. In the latter case, a C-H insertion to form a pi-allylruthenium intermediate is proposed and supported by deuterium-labeling studies. A rationale is presented for the structural dependence of the mechanism.

    View details for DOI 10.1021/ja12450c

    View details for Web of Science ID 000175369100030

    View details for PubMedID 11982367

  • An unusual ruthenium-catalyzed cycloisomerization of alkynes and propargyl alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rudd, M. T. 2002; 124 (16): 4178-4179

    Abstract

    CpRu(NCCH3)3+PF6- catalyzes the cycloisomerization of diyne-ols to alpha,beta,gamma,delta-unsaturated aldehydes and ketones in good-to-excellent yields. 1-Hydroxy-2,7-diynes and 1-hydroxy-2,8-diynes can be utilized to form highly functionalized five- and six-membered rings, respectively. Tertiary as well as secondary propargyl alcohols are cycloisomerized to a single isomeric product. A wide variety of tether substitution can be tolerated. Even totally unsubstituted tethers can be employed, as geminal disubstituents are not required for cyclization. Additional hydroxyl substituents at an alternative "internal" propargylic position are eliminated during the reaction-a feature that leads to a convenient cyclopentadiene synthesis. Furthermore, 3-hydroxy-1,6-diynes also can be cyclized to form cross-conjugated aldehydes.

    View details for DOI 10.1021/ja012672a

    View details for Web of Science ID 000175088600005

    View details for PubMedID 11960424

  • A Ru catalyzed divergence: Oxidative cyclization vs cycloisomerization of bis-homopropargylic alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rhee, Y. H. 2002; 124 (11): 2528-2533

    Abstract

    During the course of investigating the development of catalytic reactions involving ruthenium vinylidene intermediates, a novel divergence of reactivity was discovered. The oxidative cyclization of bis-homopropargylic alcohols with Ru(+2) complexes as catalysts and N-hydroxysuccinimide as oxidant, which requires formation of a ruthenium vinylidene intermediate, is complicated by the simple electrophilically initiated direct attack of the hydroxyl group on a pi-complex of the alkyne and ruthenium. A catalytic system composed of CpRu[(p-CH(3)O(6)H(4))(3)P](2)Cl and excess (p-CH(3)O-C(6)H(4))(3)P directs the reaction toward the oxidative cyclization to form delta-lactones in good yields. Significantly, a simple switch of catalyst to CpRu[(p-FC(6)H(4))(3)P](2)Cl redirects the reaction to a cycloisomerization to form dihydropyrans in good yields. The synthetic utility of the oxidative cyclization is illustrated by the synthesis of oviposition attractant pheromone of the mosquito Culex pipens. The utility of the cycloisomerization to dihydropyrans is demonstrated by an iterative process leading to the antiviral agent narbosine B. A rationale for this dramatic switch by simple ligand modification is proposed.

    View details for DOI 10.1021/ja011840w

    View details for Web of Science ID 000174435700042

    View details for PubMedID 11890802

  • Application of the AAA reaction to the synthesis of the furanoside of C-2-epi-hygromycin A: A total synthesis of C-2-epi-hygromycin A CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Dudash, J., Dirat, O. 2002; 8 (1): 259-268

    Abstract

    A strategy for stereocontrolled syntheses of furanoside type of natural products is developed for a glycosyl aryl ether. This strategy resolves the issue of low diastereoselectivity typical of normal glycosidation methods for furanosides. All the stereochemistry ultimately derives from a desymmetrization of a 2,5-diacyloxy-2,5-dihydrofuran using Pd catalyzed asymmetric allylic alkylation which sets both the absolute stereochemistry and 1,4-relative stereochemistry. Diastereo-controlled elaboration of the 3,4-double bond then completes the synthesis. A new conjunctive reagent, 1-nitro-1-phenylsulfonyl-ethane, is developed to serve as an acyl anion equivalent. The utility of a phenol as a nucleophile in the Pd catalyzed glycosylation is demonstrated. From this strategy emerged a short, practical synthesis of C-2-epi-hygromycin A.

    View details for Web of Science ID 000173248200026

    View details for PubMedID 11822457

  • Pd asymmetric allylic alkylation (AAA). A powerful synthetic tool CHEMICAL & PHARMACEUTICAL BULLETIN Trost, B. M. 2002; 50 (1): 1-14

    Abstract

    Palladium catalyzed asymmetric allylic alkylations represent a challenging problem because the mechanism of the reaction places the chiral environment distal to the bond breaking or making events responsible for the asymmetric induction. Furthermore, unlike virtually every other asymmetric process, many strategies can be employed for introduction of asymmetry and many different types of bonds can be formed. While over 100 different ligands have been designed, a family of ligands derived from 2-diphenylphosphinobenzoic or 1-naphthoic acid and chiral scalemic diamines have been successful in inducing excellent enantioselectivity by five different enantiodiscriminating events. These methods have already provided practical strategies towards numerous biological targets--some of which are adenosine and its enantiomer, aflatoxin B, aristeromycin, calanolide A and B, carbovir, cyclophellitol, ethambutol, galanthamine, mannostatin, neplanocin, phyllanthocin, sphingofungins E and F, tetraponaines, vigabatrin, and valienamine.

    View details for Web of Science ID 000173003100001

    View details for PubMedID 11824567

  • Designed ligands as probes for the catalytic binding mode in mo-catalyzed asymmetric allylic alkylation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Dogra, K., Hachiya, I., Emura, T., Hughes, D. L., Krska, S., Reamer, R. A., Palucki, M., Yasuda, N., Reider, P. J. 2002; 41 (11): 1929-?

    View details for Web of Science ID 000176045200024

    View details for PubMedID 19750636

  • Palladium-catalyzed asymmetric allylic alkylation of alpha-aryl ketones ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Schroeder, G. M., Kristensen, J. 2002; 41 (18): 3492-3495

    View details for Web of Science ID 000178177700050

    View details for PubMedID 12298076

  • Callipeltoside A: Assignment of absolute and relative configuration by total synthesis ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Dirat, O., Gunzner, J. L. 2002; 41 (5): 841-?

    View details for Web of Science ID 000174464200037

    View details for PubMedID 12491354

  • An Efficient one-pot enantio- and diastereoselective synthesis of heterocycles ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Machacek, M. R. 2002; 41 (24): 4693-4697

    View details for Web of Science ID 000180051600020

    View details for PubMedID 12481329

  • An efficient enantioselective synthesis of (-)-galanthamine ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Tang, W. P. 2002; 41 (15): 2795-?

    View details for Web of Science ID 000177382300028

    View details for PubMedID 12203489

  • A stereospecific ruthenium-catalyzed allylic alkylation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Fraisse, P. L., Ball, Z. T. 2002; 41 (6): 1059-?

    View details for Web of Science ID 000174450300035

    View details for PubMedID 12491312

  • A dinuclear Zn catalyst for the asymmetric nitroaldol (Henry) reaction ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Yeh, V. S. 2002; 41 (5): 861-?

    View details for Web of Science ID 000174464200044

    View details for PubMedID 12491361

  • Polymer-supported C-2-symmetric ligands for palladium-catalyzed asymmetric allylic alkylation reactions ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Pan, Z. Y., Zambrano, J., Kujat, C. 2002; 41 (24): 4691-4693

    View details for Web of Science ID 000180051600019

    View details for PubMedID 12481328

  • Atom economic asymmetric creation of quaternary carbon: Regio- and enantioselective reactions of a vinylepoxide with a carbon nucleophile JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Jiang, C. H. 2001; 123 (51): 12907-12908

    View details for DOI 10.1021/ja012104v

    View details for Web of Science ID 000172939700022

    View details for PubMedID 11749552

  • Markovnikov alkyne hydrosilylation catalyzed by ruthenium complexes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ball, Z. T. 2001; 123 (50): 12726-12727

    View details for DOI 10.1021/ja0121033

    View details for Web of Science ID 000172745300052

    View details for PubMedID 11741457

  • Atom economy. Aldol-type products by vanadium- catalyzed additions of allenic alcohols and aldehydes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Jonasson, C., Wucher, M. 2001; 123 (50): 12736-12737

    View details for DOI 10.1021/ja011351w

    View details for Web of Science ID 000172745300057

    View details for PubMedID 11741462

  • Synthesis of 1,1-disubstituted alkenes via a Ru-catalyzed addition JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B., Toste, F. D., Sperrle, M. 2001; 123 (50): 12504-12509

    Abstract

    The synthesis of 1,1-disubstituted alkenes typically involves reactions that lack atom economy such as olefination protocols. The use of various ruthenium complexes to effect the addition of terminal alkynes to alkenes is explored as an atom economical strategy. Two new ruthenium complexes have been discovered that effect this reaction at ambient temperature, cyclopentadienylruthenium (triphenylphosphine) camphorsulfonate and cyclopentadienylruthenium tris(acetonitrile) hexafluorophosphate. Using these complexes as catalysts, reactions proceed at ambient temperature in acetone or DMF, respectively. Regioselectivity favoring the formation of a 1,1-disubstituted over a 1,2-disubstituted alkene typically ranges from 9:1 to >25:1. The reaction demonstrates extraordinary chemoselectivity-even di- and trisubstituted alkenes such as present in the products do not compete with the starting monosubstituted alkene. Free hydroxyl groups as well as silyl and PMB ethers are tolerated as are ketones, esters, and amides. The mechanism of the reaction is believed to invoke formation of a metallacyclopentene. To account for the chemo- and regioselectivity, the initial formation of the metallacycle is believed to be reversible. While formation of the 2,5-disubstituted ruthenacyclopentene, which produces the linear product, is believed to be kinetically preferred, the rate of beta-hydrogen elimination from the 2,4-disubstituted ruthenacyclopentene, which produces the branched product, is believed to be faster. Thus, the competition between the rate of beta-hydrogen elimination and cycloreversion rationalizes the results.

    View details for DOI 10.1021/ja012009m

    View details for Web of Science ID 000172745300008

    View details for PubMedID 11741413

  • Ruthenium-catalyzed two-component addition to form 1,3-dienes: Optimization, scope, applications, and mechanism JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B., Seidel, M. 2001; 123 (50): 12466-12476

    Abstract

    A two component coupling of an allene and an activated olefin to form 1,3-dienes has been developed. The requisite allenes are synthesized either from terminal alkynes by a one carbon homologation using copper(I) iodide, paraformaldehyde, and diisopropylamine, via an ortho ester-Claisen rearrangement from a propargylic alcohol, or via a Wittig type reaction on a ketene generated in situ from an acid chloride. Mono- through tetrasubstituted allenes could be synthesized by these methods. Either cyclopentadienylruthenium(II) cyclooctadiene chloride or cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate catalyze the addition reaction. When the former catalyst is employed, an alkyne activator is added to help generate the active catalyst. Through systematic optimization studies, a range of conditions was examined. The optimal conditions consisted of the use of cerium(III) trichloride heptahydrate as a cocatalyst in dimethylformamide as a solvent at 60 degrees C. The reaction was found to be chemoselective, and a wide range of functionality was tolerated, including esters, alcohols, nitriles, and amides. When substituted allenes are used, good selectivity can be obtained with proper substitution. A mechanism involving a ruthenacycle is proposed to account for the selectivity or lack thereof in product formation. With disubstituted allenes, selectivity is obtained when beta-hydrogen elimination is favored from a specific site. In tri- and tetrasubstituted allenes, steric issues concerning the C-C bond forming event appear to be the dominant factor in determining product formation. This process represents a highly atom-economical synthesis of 1,3-dienes in a controlled fashion. The utility of the 1,3-diene products was demonstrated by their use in Diels-Alder reactions to form a variety of cyclic systems including polycyclic structures. This sequence represents a convergent atom economic method for ring formation by a series of simple additions.

    View details for DOI 10.1021/ja011428g

    View details for Web of Science ID 000172745300004

    View details for PubMedID 11741409

  • gem-diacetates as carbonyl surrogates for asymmetric synthesis. Total syntheses of sphingofungins E and F JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lee, C. B. 2001; 123 (49): 12191-12201

    Abstract

    The equivalent of an asymmetric addition to a carbonyl group with a stabilized anion is accomplished by discriminating between the enantiotopic C-O single bonds of a gem-diacetate. In this way, enantioselective total syntheses of two antifugal agents, sphingofungins E and F, have been accomplished. The synthetic strategy is based on a series of catalytic processes whereby all of the chiral centers are created with high stereoselectivities. The first two stereocenters are introduced by an asymmetric allylic alkylation reaction of gem-diacetate 9 with azlactone 10. The complex of Pd(0) and ligand 14 efficiently catalyzes this key reaction, which differentiates both the enantiotopic leaving groups of a gem-diacetate and enantiotopic faces of the enolate of an azlactone in high enantiomeric excess and diastereomeric excess. From these two stereocenters, the configurations of the remaining two centers are set by a diastereoselective Os(VIII)-catalyzed dihydroxylation reaction with excellent stereocontrol. The trans-alkene is established by Cr(II)-mediated olefination, and a subsequent B-alkyl Suzuki coupling reaction conjoins the polar head unit and the nonpolar, 13-carbon lipid tail. The efficiency of our strategy is illustrated by the completion of syntheses of sphingofungins F and E in 15 and 17 steps, and in 17% and 5% overall yields, respectively.

    View details for DOI 10.1021/ja0118338

    View details for Web of Science ID 000172645100009

    View details for PubMedID 11734018

  • A three-component coupling approach to cyclopentanoids JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Pinkerton, A. B. 2001; 66 (23): 7714-7722

    Abstract

    A new approach to 2,3-disubstituted cyclopentenones has been developed. This approach consists of a two-step protocol involving the cyclization of a Z-vinyl bromide under Barbier type conditions to form a cyclopentenol, which is then oxidatively rearranged to generate the cyclopentenone. The Z-vinyl bromide is in turn derived from a ruthenium catalyzed three-component coupling of an alkyne, an enone, and a HBr equivalent. A range of 2,3-disubstituted cyclopentenones has been generated, including short syntheses of jasmone and dihydrojasmone. Further applicability of this strategy is shown in the total syntheses of tetrahydrodicranenone B, rosaprostol, and a selective COX-2 inhibitor.

    View details for DOI 10.1021/jo010593b

    View details for Web of Science ID 000172174800021

    View details for PubMedID 11701026

  • An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient formal synthesis of LY 333531 ORGANIC LETTERS Trost, B. M., Tang, W. P. 2001; 3 (21): 3409-3411

    Abstract

    [reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a palladium-catalyzed dynamic kinetic asymmetric transformation leads to an efficient synthesis of a selective PKC inhibitor under clinical development.

    View details for Web of Science ID 000171708000046

    View details for PubMedID 11594846

  • Total synthesis of deschlorocallipeltoside A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Gunzner, J. L. 2001; 123 (38): 9449-9450

    View details for DOI 10.1021/ja011424b

    View details for Web of Science ID 000171169700031

    View details for PubMedID 11562231

  • An unusual ruthenium-catalyzed dimerization of propargyl alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Rudd, M. T. 2001; 123 (36): 8862-8863

    View details for Web of Science ID 000170925400031

    View details for PubMedID 11535098

  • AAA in KAT/DYKAT processes: First- and second-generation asymmetric syntheses of (+)- and (-)-cyclophellitol CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Patterson, D. E., Hembre, E. J. 2001; 7 (17): 3768-3775

    Abstract

    Kinetic resolutions and kinetic asymmetric transformations (KAT) as well as dynamic kinetic resolutions and dynamic kinetic asymmetric transformations (DYKAT) are important synthetic protocols. The feasibility of KAT and DYKAT processes for asymmetric allylic alkylations (AAA) is explored utilizing a single substrate--conduritol B tetraesters. Both processes can be performed resulting in excellent enantioselectivity. The impact of nucleophile and leaving group on the effectiveness of each is outlined. The ability to differentiate the various hydroxyl groups is also described. For this purpose, 4-tert-butyldimethylsiloxy-2,2-dimethylbutyric acid was developed as a nucleophile. The utility of effecting KAT/DYKAT processes through the Pd-catalyzed AAA reaction is demonstrated by efficient syntheses of both enantiomers of the potent glycosidase inhibitor cyclophellitol.

    View details for Web of Science ID 000170914500015

    View details for PubMedID 11575778

  • Direct asymmetric aldol reactions of acetone using bimetallic zinc catalysts ORGANIC LETTERS Trost, B. M., Silcoff, E. R., Ito, H. 2001; 3 (16): 2497-2500

    Abstract

    [reaction: see text] The enantioselective aldol reaction using a novel binuclear zinc catalyst of acetone with several aldehydes gave products in good yields (62-89%) with a high level of enantioselectivity (ee = 76-92%).

    View details for DOI 10.1021/ol0161211

    View details for Web of Science ID 000170392300020

    View details for PubMedID 11483044

  • A catalytic asymmetric Wagner-Meerwein shift JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Yasukata, T. 2001; 123 (29): 7162-7163

    View details for DOI 10.1021/ja010504c

    View details for Web of Science ID 000169978900025

    View details for PubMedID 11459498

  • Non-metathesis ruthenium-catalyzed C-C bond formation CHEMICAL REVIEWS Trost, B. M., Toste, F. D., Pinkerton, A. B. 2001; 101 (7): 2067-2096

    View details for DOI 10.1021/cr000666b

    View details for Web of Science ID 000170045000009

    View details for PubMedID 11710241

  • An unusual regioselectivity in the Pd-catalyzed cross coupling of alkynes. A correction TETRAHEDRON LETTERS Trost, B. M., Gunzner, J. L., Yasukata, T. 2001; 42 (23): 3775-3778
  • Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part I. Asymmetric addition of malonate nucleophiles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lee, C. B. 2001; 123 (16): 3671-3686

    Abstract

    Asymmetric alkylations of allylic geminal dicarboxylates with dialkyl malonates have been investigated. The requisite allylic geminal dicarboxylates are prepared in good yields and high isomeric purities by two catalytic methods, ferric chloride-catalyzed addition of acid anhydrides to alpha,beta-unsaturated aldehydes and palladium-catalyzed isomerization and addition reactions of propargylic acetates. The complex of palladium(0) and the chiral ligand derived from the diamide of trans-1,2-diaminocyclohexane and 2-diphenylphosphinobenzoic acid most efficiently catalyzed the asymmetric process to provide allylic carboxylate esters with high ee. By systematic optimization studies, factors affecting the enantioselectivity of the reaction have been probed. In general, higher ee's have been achieved with those conditions which facilitate kinetic capture of the incipient pi-allylpalladium intermediate. These conditions also proved effective for achieving high regioselectivities. The minor regioisomeric product was formed when reactive substrates or achiral ligands were employed for the reaction, and could be minimized through the use of the chiral ligand. Under the established conditions, the alkylation of various gem-dicarboxylates afforded monoalkylated products in high yields with greater than 90% ee. The process constitutes the equivalent of an addition of a stabilized nucleophile to a carbonyl group with high asymmetric induction.

    View details for DOI 10.1021/ja003774o

    View details for Web of Science ID 000168442500007

    View details for PubMedID 11457099

  • Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part II. Scope and applications JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lee, C. B. 2001; 123 (16): 3687-3696

    Abstract

    An enantioselective synthesis of allylic esters has been achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently induced the alkylation process with a variety of nucleophiles to provide allylic esters as products in good yield. High regio- and enantioselectivities were observed in the alkylation with most nucleophiles derived from malonate, whereas a modest level of ee's was obtained in the reactions with less reactive nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow addition procedure proved effective, leading to significantly improved ee's. The utility of the alkylation products was demonstrated by several synthetically useful transformations including allylic isomerizations, allylic alkylations, and Claisen rearrangements. Using these reactions, the chirality of the initial allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds in a predictable fashion with high stereochemical fidelity. The conversion of gem-diesters to chiral esters by the substitution reaction is the equivalent of an asymmetric carbonyl addition by stabilized nucleophiles. In conjunction with the subsequent reactions that occur with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a double allylic transformation.

    View details for Web of Science ID 000168442500008

    View details for PubMedID 11457100

  • Asymmetric induction of conduritols via AAA reactions: Synthesis of the aminocyclohexitol of hygromycin A CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Dudash, J., Hembre, E. J. 2001; 7 (8): 1619-1629

    Abstract

    Two synthetic routes towards the construction of the aminocyclohexitol moiety of hygromycin A have been developed based on palladium-catalyzed asymmetric alkylation of conduritol derivatives. A protocol has been established whereby this biologically relevant molecule is formed from benzoquinone. A conduritol A derivative is synthesized in eight steps from benzoquinone and is then subjected to the palladium reaction. From this flexible intermediate, four epimers of the aminocyclitol, including the natural one, can be obtained with complete stereoselectivity. Racemic conduritol B derivatives are available in four steps from benzoquinone, and these are then made enantiomerically pure by a palladium-catalyzed dynamic kinetic resolution. From the chiral conduritol B, the aminocyclitol is available in six steps. Excellent levels of enantio- and diastereoselectivity highlight these strategies.

    View details for Web of Science ID 000168368500007

    View details for PubMedID 11349902

  • Asymmetric aldol reaction via a dinuclear zinc catalyst: alpha-hydroxyketones as donors JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ito, H., Silcoff, E. R. 2001; 123 (14): 3367-3368

    View details for Web of Science ID 000168078500022

    View details for PubMedID 11457073

  • An atom-economical three-carbon chain extension of alkynes to form E-enol silanes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Surivet, J. P., Toste, F. D. 2001; 123 (12): 2897-2898

    View details for Web of Science ID 000167792400029

    View details for PubMedID 11456983

  • Atom economy: Aldol-type products by vanadium-catalyzed additions of propargyl alcohols and aldehydes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Oi, S. 2001; 123 (6): 1230-1231

    View details for DOI 10.1021/ja003629a

    View details for Web of Science ID 000166873000025

    View details for PubMedID 11456678

  • An Atom-Economic Three-Carbon Chain Extension to Give Enamides We thank the National Science Foundation and the National Institutes of Health, General Medical Sciences, for their generous support of our programs and Rhône-Poulenc for partial financial support for J.P.S. Mass spectra were provided by the Mass Spectrometry Facility of the University of California, San Francisco, supported by the NIH Division of Research Resources. Angewandte Chemie (International ed. in English) Trost, B. M., Surivet, J. P. 2001; 40 (8): 1468–71

    View details for PubMedID 11317305

  • Constructing tricyclic compounds containing a seven-membered ring by ruthenium-catalyzed intramolecular [5+2] cycloaddition ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Shen, H. C. 2001; 40 (12): 2313-?
  • On the source of transfer of stereochemical information in ligands for Pd-catalyzed AAA reactions SYNLETT Trost, B. M., Zambrano, J. L., Richter, W. 2001: 907-909
  • Synthesis of the first (1-3 : 6,7-eta-cyclodecadienyl)ruthenium complex by the intramolecular reaction of an alkene and a vinylcyclopropane ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Toste, F. D. 2001; 40 (6): 1114-?
  • An atom-economic three-carbon chain extension to give enamides ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Surivet, J. P. 2001; 40 (8): 1468-?
  • An asymmetric synthesis of C-2-epi-hygromycin A ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Dirat, O., Dudash, J., Hembre, E. J. 2001; 40 (19): 3658-?
  • An Atom-Economic Three-Carbon Chain Extension to Give Enamides. Angewandte Chemie (International ed. in English) Trost, B. M., Surivet, J. P. 2001; 40 (8): 1468–71

    Abstract

    Di- or trisubstituted alkenes of defined geometry, with terminal enamide groups, are formed in an atom-economic three-carbon chain extension of alkynes with allyl amides catalyzed by ruthenium (see, for example, Equation (1); Boc=tert-butoxycarbonyl, TMS=trimethylsilyl).

    View details for PubMedID 29712378

  • Constructing Tricyclic Compounds Containing a Seven-Membered Ring by Ruthenium-Catalyzed Intramolecular [5+2] Cycloaddition. Angewandte Chemie (International ed. in English) Trost, B. M., Shen, H. C. 2001; 40 (12): 2313–16

    Abstract

    Efficient access to tricyclic compounds such as 2 and 3, which contain a seven-membered ring, is provided by the ruthenium-catalyzed intramolecular [5+2] cycloaddition of a 1,2,3-trisubstituted cyclopropyl enyne such as 1. Improved regioselectivity is observed when In(OTf)3 is used as the cocatalyst. (No cocatalyst: 2:3 6:1; cat. In(OTf)3 (10 %): 2:3 >20:1; Tf=trifluoromethanesulfonyl).

    View details for PubMedID 29711821

  • An Asymmetric Synthesis of C-2-epi-Hygromycin A We thank the National Science Foundation and the National Institute of Health, General Medical Sciences, for their generous support of our programs. O.D. thanks the Association pour la Recherche contre le Cancer (ARC) for a postdoctoral fellowship. Mass spectra were kindly provided by the Mass Spectrometry Facility, University of San Francisco, supported by the NIH Division of Research Resources. Angewandte Chemie (International ed. in English) Trost, B. M., Dirat, O., Dudash Jr, J., Hembre, E. J. 2001; 40 (19): 3658–60

    View details for PubMedID 11592213

  • Synthesis of the First (1-3:6,7-eta-Cyclodecadienyl)ruthenium Complex by the Intramolecular Reaction of an Alkene and a Vinylcyclopropane We thank the National Science Foundation and the National Institutes of Health (NIH), General Medical Sciences, for their generous support of our programs. We are grateful to A. Cole for solving the X-ray structure of 3. Mass spectra were provided by the Mass Spectrometry Facility of the University of California, San Francisco, supported by the NIH Division of Research Resources. Angewandte Chemie (International ed. in English) Trost, B. M., Toste, F. D. 2001; 40 (6): 1114–16

    View details for PubMedID 11268093

  • Constructing Tricyclic Compounds Containing a Seven-Membered Ring by Ruthenium-Catalyzed Intramolecular Angewandte Chemie (International ed. in English) Trost, B. M., Shen, H. C. 2001; 40 (12): 2313–16

    View details for PubMedID 11433506

  • Asymmetric synthesis of quaternary centers. Total synthesis of (-)-malyngolide ORGANIC LETTERS Trost, B. M., Tang, W. P., Schulte, J. L. 2000; 2 (25): 4013-4015

    Abstract

    [structure] The deracemization of 3-nonyl-3,4-epoxybut-1-ene with Pd(0) in the presence of chiral ligands using p-methoxybenzyl alcohol as a nucleophile proceeds regio- and enantioselectively to form the monoprotected vinylglycidol in 99% ee. This chiral building block was converted in seven steps to (-)-malyngolide, an antibiotic showing significant activity against Mycobacterium smegmatis and Streptococcus pyogenes. An interesting aspect involves controlling the diastereoselectivity of protonation of an enolate via a distal hydroxyl group.

    View details for Web of Science ID 000165829200016

    View details for PubMedID 11112631

  • A ruthenium-catalyzed pyrrolidine and piperidine synthesis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B., Kremzow, D. 2000; 122 (48): 12007-12008
  • A direct catalytic enantioselective aldol reaction via a novel catalyst design JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Ito, H. 2000; 122 (48): 12003-12004
  • Enhanced geometrical control in a Ru-catalyzed three component coupling TETRAHEDRON LETTERS Trost, B. M., Pinkerton, A. B. 2000; 41 (49): 9627-9631
  • Atom economical syntheses of oxygen heterocycles via tandem palladium-catalyzed reactions JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Frontier, A. J. 2000; 122 (47): 11727-11728
  • Enantioselective total synthesis of (-)-galanthamine JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 2000; 122 (45): 11262-11263

    View details for DOI 10.1021/ja002231b

    View details for Web of Science ID 000165337800042

  • A Ru-catalyzed four-component coupling JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B. 2000; 122 (33): 8081-8082
  • On the regioselectivity of the Ru-catalyzed intramolecular [5+2] cycloaddition ORGANIC LETTERS Trost, B. M., Shen, H. C. 2000; 2 (16): 2523-2525

    Abstract

    The influence of substituents on which cyclopropyl bond cleaves in the cycloisomerization of cyclopropylenynes catalyzed by CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving bond appears to be an important factor. With cis cyclopropyl substrates, steric effects appear to dominate.

    View details for DOI 10.1021/ol0061945

    View details for Web of Science ID 000088605200034

    View details for PubMedID 10956537

  • Diastereo- and enantioselective allylation of substituted nitroalkanes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Surivet, J. P. 2000; 122 (26): 6291-6292
  • alpha-acetoxysulfones as "chiral aldehyde" equivalents JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Crawley, M. L., Lee, C. B. 2000; 122 (25): 6120-6121

    View details for DOI 10.1021/ja000627h

    View details for Web of Science ID 000088054900029

  • A ruthenium-catalyzed hydrative cyclization and [4+2] cycloaddition of yne-enones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., BROWN, R. E., Toste, F. D. 2000; 122 (24): 5877-5878
  • A regioselective Ru-catalyzed alkene-alkyne coupling ORGANIC LETTERS Trost, B. M., Machacek, M., Schnaderbeck, M. J. 2000; 2 (12): 1761-1764

    Abstract

    [reaction: see text] The reaction of silylalkynes and terminal alkenes proceeds with complete control of regioselectivity by the silyl substituent to give geometrically defined vinylsilanes. Since terminal alkynes normally give mixtures, protodesilylation of these adducts then constitutes a regioselective addition of terminal alkynes to terminal alkenes.

    View details for Web of Science ID 000087525300029

    View details for PubMedID 10880220

  • A new strategy for cyclopentenone synthesis ORGANIC LETTERS Trost, B. M., Pinkerton, A. B. 2000; 2 (11): 1601-1603

    Abstract

    [reaction--see text] A new strategy for the synthesis of 2,3-disubstituted cyclopentenones emerges from two key reactions-the ruthenium-catalyzed three-component coupling of an equivalent of HBr, an alkyne, and a vinyl ketone and the Ni-Cr Barbier type reaction. As a result, these important structures are readily accessed from an alkyne and a vinyl ketone (which derive directly from carboxylic acids). Syntheses of tetrahydrodicranenone B and rosaprostol illustrate the new strategy.

    View details for Web of Science ID 000087292600027

    View details for PubMedID 10841489

  • Cyclic 1,2-diketones as building blocks for asymmetric synthesis of cycloalkenones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Schroeder, G. M. 2000; 122 (15): 3785-3786
  • Deracemization of Baylis-Hillman adducts JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Tsui, H. C., Toste, F. D. 2000; 122 (14): 3534-3535
  • Ruthenium-catalyzed intramolecular [5+2] cycloadditions JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D., Shen, H. 2000; 122 (10): 2379-2380
  • Palladium-catalyzed asymmetric allylic alkylation of barbituric acid derivatives: Enantioselective syntheses of cyclopentobarbital and pentobarbital JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Schroeder, G. M. 2000; 65 (5): 1569-1573

    View details for Web of Science ID 000085913800045

    View details for PubMedID 10814127

  • Ruthenium-catalyzed cycloisomerizations of 1,6- and 1,7-enynes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 2000; 122 (4): 714-715
  • A Mechanistic Dichotomy Leading to a Ruthenium-Catalyzed cis-Addition for Stereoselective Formation of (Z)-Vinyl Bromides. Angewandte Chemie (International ed. in English) Trost, B. M., Pinkerton, A. B. 2000; 39 (2): 360–62

    Abstract

    Either trans- or cis-haloalkylation is possible through a three-component coupling [Eq. (1)]. The cis-bromoruthenation of an alkyne by lithium bromide and [CpRu(CH(3)CN)(3)]PF(6), catalyzed by SnBr(4), gives (Z)-vinyl bromides with high chemoselectivity. The degree of control over the sterochemistry raises intriguing mechanistic questions as well as offering practical synthetic utility.

    View details for PubMedID 10649409

  • Asymmetric alkylation of nitroalkanes ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Surivet, J. P. 2000; 39 (17): 3122-3124
  • A mechanistic dichotomy leading to a ruthenium-catalyzed cis-addition for stereoselective formation of (Z)-vinyl bromides ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Pinkerton, A. B. 2000; 39 (2): 360-?
  • Asymmetric Alkylation of Nitroalkanes We thank the National Science Foundation and the National Institutes of Health (NIH), General Medical Sciences, for their generous support of our programs. Rhône-Poulenc graciously provided a postdoctoral fellowship for J.-P. S. Mass spectra were provided by the Mass Spectrometry Facility of the University of California, San Francisco, supported by the NIH Division of Research Resources. Angewandte Chemie (International ed. in English) Trost, B. M., Surivet, J. P. 2000; 39 (17): 3122–24

    View details for PubMedID 11028053

  • Dynamic kinetic asymmetric transformations of conduritol B tetracarboxylates: An asymmetric synthesis of D-myo-inositol 1,4,5-trisphosphate JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Patterson, D. E., Hembre, E. J. 1999; 121 (46): 10834-10835
  • A ruthenium-catalyzed alkylative cycloetherification JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B. 1999; 121 (46): 10842-10843
  • Regio- and enantioselective molybdenum-catalyzed alkylations of polyenyl esters JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Hildbrand, S., Dogra, K. 1999; 121 (44): 10416-10417
  • cis-5-amino-6-hydroxycyclohexadiene as a chiral building block: An asymmetric synthesis of (-)-swainsonine CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Patterson, D. E. 1999; 5 (11): 3279-3284
  • A new Ru catalyst for alkene-alkyne coupling TETRAHEDRON LETTERS Trost, B. M., Toste, F. D. 1999; 40 (44): 7739-7743
  • Ruthenium-catalyzed cycloisomerization of 1,6-enynes initiated by C-H activation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 1999; 121 (41): 9728-9729
  • Chiral recognition for control of alkene geometry in a transition metal catalyzed allylic alkylation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Heinemann, C., Ariza, X., Weigand, S. 1999; 121 (37): 8667-8668
  • Inorganic carbonates as nucleophiles for the asymmetric synthesis of vinylglycidols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., McEachern, E. J. 1999; 121 (37): 8649-8650
  • Palladium-catalyzed asymmetric alkylation of ketone enolates JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Schroeder, G. M. 1999; 121 (28): 6759-6760
  • On the synthesis of Z-gamma-amino-alpha,beta-unsaturated esters via Ru-catalyzed coupling ORGANIC LETTERS Trost, B. M., Roth, G. J. 1999; 1 (1): 67-70

    Abstract

    [formula: see text] A synthesis of gamma-amino acids and their cyclic derivatives, 3-pyrrolinones, from alpha-amino acids employs a ruthenium-catalyzed Alder ene reaction as a key step in the sequence. Cyclopentadienylruthenium (1,4-cyclooctadiene) chloride catalyzes the addition of gamma-amido-alpha,beta-alkynoate esters with monosubstituted alkenes. The major product arises from C-C bond formation at the alpha-carbon of the alkynoate. The reaction exhibits high chemoselectivity. The ruthenium-catalyzed addition occurs in preference to a Diels-Alder reaction. The two new double bonds are created with complete geometrical control. The initial gamma-amido-alpha,beta-unsaturated ester can be cyclized to the pyrrolinones with a tin catalyst.

    View details for Web of Science ID 000083701300018

    View details for PubMedID 10822535

  • A ruthenium-catalyzed two-component addition to form 1,3-dienes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B. 1999; 121 (16): 4068-4069
  • Palladium-catalyzed kinetic and dynamic kinetic asymmetric transformation of 5-acyloxy-2-(5H)-furanone. Enantioselective synthesis of (-)-aflatoxin B lactone JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 1999; 121 (14): 3543-3544
  • A ruthenium-catalyzed three-component coupling to form E-vinyl chlorides JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Pinkerton, A. B. 1999; 121 (9): 1988-1989
  • Novel chiral bidentate eta(5)-cyclopentadienylphosphine ligands: Their asymmetric induction at the ruthenium(II) center and application in catalysis CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M., Vidal, B., Thommen, M. 1999; 5 (3): 1055-1069
  • Pd catalyzed kinetic resolution of conduritol B. Asymmetric synthesis of (+)-cyclophellitol TETRAHEDRON LETTERS Trost, B. M., Hembre, E. J. 1999; 40 (2): 219-222
  • Total Synthesis of (+)-Saponaceolide B. Angewandte Chemie (International ed. in English) Trost, B. M., Corte, J. R. 1999; 38 (24): 3664–66

    Abstract

    Coupling of three fragments results in the first total synthesis of a saponaceolide (see scheme). The first fragment, the spiroketal portion, is formed from two moieties, one derived from geraniol and the other from allyl malonate. A sulfone alkylation-desulfonylation sequence joins the spiroketal portion to the methylene-3,3-dimethylcyclohexane unit. The subsequent stereoselective Wittig reaction attaches the final piece to complete the synthesis of saponaceolide B (1), one of the most biologically active members of this family.

    View details for PubMedID 10649317

  • An asymmetric synthesis of the vitamin E core by Pd catalyzed discrimination of enantiotopic alkene faces SYNTHESIS-STUTTGART Trost, B. M., Asakawa, N. 1999: 1491-1494
  • Total synthesis of (+)-saponaceolide B ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Corte, J. R. 1999; 38 (24): 3664-3666
  • Towards the total synthesis of saponaceolides: Synthesis of cis-2,4-disubstituted 3,3-dimethylmethylenecyclohexanes ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Corte, J. R., Gudiksen, M. S. 1999; 38 (24): 3662-3664
  • A Versatile Enantioselective Strategy Toward L-C-Nucleosides: A Total Synthesis of L-Showdomycin. The Journal of organic chemistry Trost, B. M., Kallander, L. S. 1999; 64 (15): 5427–35

    Abstract

    Strategies for the synthesis of nucleosides that can provide either L or D isomers become more important as a result of the increasing number of such compounds that are therapeutically useful. The lower toxicity and reduced susceptibility toward metabolism of the L isomers make them particularly interesting. A strategy toward the C-nucleoside analogues has been explored in the context of the synthesis of L-showdomycin. The route involves an asymmetric desymmetrization using palladium catalysis of cis-2,5-diacyloxy-2,5-dihydrofurans available in one step from furan, with carbon nucleophiles. Nucleophilic synthons for a maleimide unit and a methoxycarbonyl unit have been designed. Two sequential palladium-catalyzed reactions introduce both substituents with excellent chemo-, regio-, diastereo-, and enantioselectivity. The presence of a double bond in this doubly alkylated compound at C-3 and C-4 allows easy structural variation. The use of an ester as a hydroxymethyl precursor also introduces a diversity element as well as having importance in its own right. The successful completion of a synthesis of L-showdomycin validates this approach as a viable strategy to C-nucleosides.

    View details for PubMedID 11674603

  • Towards the Total Synthesis of Saponaceolides: Synthesis of cis-2,4-Disubstituted 3,3-Dimethylmethylenecyclohexanes. Angewandte Chemie (International ed. in English) Trost, B. M., Corte, J. R., Gudiksen, M. S. 1999; 38 (24): 3662–64

    Abstract

    Controlling diastereoselectivity by metal coordination: In the case of 3,3-dimethylmethylenecyclohexanes 2-a structural unit present in many interesting natural products-the thermodynamically less stable cis-2,4-disubstituted compounds become available through a cyclization event wherein the configuration is determined by a carbopalladation step. Both the cycloisomerization of 1,7-enynes 1 and the intramolecular Heck-type reaction of compounds of type 3 provide the cis product as the major product.

    View details for PubMedID 10649316

  • A two-component catalyst system for asymmetric allylic alkylations with alcohol pronucleophiles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., McEachern, E. J., Toste, F. D. 1998; 120 (48): 12702-12703
  • When is a proton not a proton? CHEMISTRY-A EUROPEAN JOURNAL Trost, B. M. 1998; 4 (12): 2405-2412
  • A catalytic enantioselective approach to chromans and chromanols. A total synthesis of (-)-calanolides A and B and the vitamin E nucleus JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 1998; 120 (35): 9074-9075
  • A route to Z-enediynes via Pd catalyzed alkyne additions TETRAHEDRON LETTERS Trost, B. M., Hachiya, I., McIntosh, M. C. 1998; 39 (36): 6445-6448
  • A new strategy for the synthesis of sphingosine analogues. Sphingofungin F JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Lee, C. B. 1998; 120 (27): 6818-6819
  • Novel polymer-supported trialkylsilanes and their use in solid-phase organic synthesis JOURNAL OF ORGANIC CHEMISTRY Hu, Y. H., Porco, J. A., Labadie, J. W., Gooding, O. W., Trost, B. M. 1998; 63 (13): 4518-4521
  • Transformations of the picrotoxanes: The synthesis of corianin and structural analogues from picrotoxinin TETRAHEDRON Krische, M. J., Trost, B. M. 1998; 54 (25): 7109-7120
  • Total synthesis of methyl picrotoxate via the palladium catalyzed enyne cycloisomerization reaction TETRAHEDRON Krische, M. J., Trost, B. M. 1998; 54 (15): 3693-3704
  • Novel polymer-supported trialkylsilane linkers and their use in solid-phase organic synthesis. Hu, Y. H., Porco, J. A., Labadie, J. W., Gooding, O. W., Trost, B. M. AMER CHEMICAL SOC. 1998: U84–U84
  • Catalyst controlled diastereoselective N-alkylations of alpha-amino esters TETRAHEDRON LETTERS Trost, B. M., Calkins, T. L., Oertelt, C., Zambrano, J. 1998; 39 (13): 1713-1716
  • Enhanced enantioselectivity in the desymmetrization of meso-biscarbamates JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Patterson, D. E. 1998; 63 (4): 1339-1341
  • Asymmetric molybdenum-catalyzed alkylations JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Hachiya, I. 1998; 120 (5): 1104-1105
  • Asymmetric O- and C-alkylation of phenols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Toste, F. D. 1998; 120 (4): 815-816
  • Transition metal catalyzed cycloisomerizations SYNLETT Trost, B. M., Krische, M. J. 1998: 1-16
  • Catalytic asymmetric alkylation of nucleophiles: Asymmetric synthesis of alpha-alkylated amino acids ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Ariza, X. 1997; 36 (23): 2635-2637
  • A convergent synthesis of (+)-parviflorin, (+)-squamocin K, and (+)-5S-hydroxyparviflorin ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., Calkins, T. L., Bochet, C. G. 1997; 36 (23): 2632-2635
  • Nitrogen pronucleophiles in the phosphine-catalyzed gamma-addition reaction JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Dake, G. R. 1997; 62 (17): 5670-5671
  • Short Preparation of (S)-(E)-1-(O-Methylmandeloxy)butadiene. The Journal of organic chemistry Trost, B. M., Chupak, L. S., Lübbers, T. 1997; 62 (3): 736

    View details for PubMedID 11671474

  • Designing a receptor for molecular recognition in a catalytic synthetic reaction: Allylic Alkylation ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M. 1996; 29 (8): 355-364
  • SYNTHETIC METHOD FOR DEHYDROGENATION OF CARBONYL AND RELATED-COMPOUNDS - A CITATION-CLASSIC COMMENTARY ON NEW SYNTHETIC REACTION - SULFENYLATIONS AND DEHYDROSULFENYLATIONS OF ESTERS AND KETONES BY TROST,B.M., SALZMANN,T.N., AND HIROI,L. CURRENT CONTENTS/ENGINEERING TECHNOLOGY & APPLIED SCIENCES Trost, B. M. 1992: 11-11
  • SYNTHETIC DEHYDROGENATION OF CARBONYL AND RELATED-COMPOUNDS - A CITATION-CLASSIC COMMENTARY ON NEW SYNTHETIC REACTION - SULFENYLATIONS AND DEHYDROSULFENYLATIONS OF ESTERS AND KETONES BY TROST,B.M., SALZMANN,T.Z., AND HIROI,L. CURRENT CONTENTS/PHYSICAL CHEMICAL & EARTH SCIENCES Trost, B. M. 1992: 11-11
  • ATOM ECONOMY - A SIMPLE PD CATALYZED ADDITION OF PRONUCLEOPHILES WITH DIENES TETRAHEDRON LETTERS Trost, B. M., Zhi, L. 1992; 33 (14): 1831-1834
  • ASYMMETRIC LIGANDS FOR TRANSITION-METAL-CATALYZED REACTIONS - 2-DIPHENYLPHOSPHINOBENZOYL DERIVATIVES OF C2-SYMMETRICAL DIOLS AND DIAMINES ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M., VANVRANKEN, D. L. 1992; 31 (2): 228-230
  • CYCLIZATIONS MADE EASY BY TRANSITION-METAL CATALYSTS SYMP ON HOMOGENEOUS TRANSITION METAL CATALYZED REACTIONS, AT THE 199TH NATIONAL MEETING OF THE AMERICAN CHEMICAL SOC Trost, B. M. AMER CHEMICAL SOC. 1992: 463–478
  • SYNTHESIS AND PALLADIUM-CATALYZED CYCLOADDITION OF THE BIFUNCTIONAL CONJUNCTIVE REAGENT METHYL (Z)-1-METHYL-2-TRIMETHYLSILYLMETHYL-2-BUTENYL CARBONATE SYNTHESIS-STUTTGART Trost, B. M., Matelich, M. C. 1992: 151-156
  • THE ATOM ECONOMY - A SEARCH FOR SYNTHETIC EFFICIENCY SCIENCE Trost, B. M. 1991; 254 (5037): 1471-1477

    Abstract

    Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.

    View details for Web of Science ID A1991GT90300030

    View details for PubMedID 1962206

  • A CONVENIENT SYNTHESIS OF N-TOSYLIMINES JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Marrs, C. 1991; 56 (22): 6468-6470
  • SYNTHESIS OF ALLOSAMIDIN JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS Maloisel, J. L., Vasella, A., Trost, B. M., VANVRANKEN, D. L. 1991: 1099-1101
  • MECHANISTIC DICHOTOMIES IN PD CATALYZED ENYNE METATHESIS OF CYCLIC OLEFINS TETRAHEDRON LETTERS Trost, B. M., Trost, M. K. 1991; 32 (30): 3647-3650
  • A CHEMOSELECTIVE INTERNAL REDOX OF ALLYL ALCOHOLS TO SATURATED ALDEHYDES OR KETONES TETRAHEDRON LETTERS Trost, B. M., Kulawiec, R. J. 1991; 32 (26): 3039-3042
  • REGIOSELECTIVE JOINING OF PRENYL UNITS - A SIMPLE STRATEGY FOR GEOMETRY CONTROL IN PD CATALYZED ALLYLIC ALKYLATIONS TETRAHEDRON LETTERS Trost, B. M., Granja, J. R. 1991; 32 (20): 2193-2196
  • A CONVENIENT SYNTHESIS OF GAMMA-HYDROXY ALPHA,BETA-UNSATURATED SULFONES JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Grese, T. A. 1991; 56 (9): 3189-3192
  • AN ASYMMETRIC-SYNTHESIS OF (+)-PHYLLANTHOCIN TETRAHEDRON LETTERS Trost, B. M., Kondo, Y. 1991; 32 (13): 1613-1616
  • AN ASYMMETRIC APPROACH TO 2-DEOXYNUCLEOSIDES VIA ORGANOSULFUR BUILDING-BLOCKS AS CHEMICAL CHAMELEONS CARBOHYDRATE RESEARCH Trost, B. M., NUBLING, C. 1990; 202: 1-12

    Abstract

    An asymmetric synthesis of 6-N-benzoyl-5'-O-benzyl-2'-deoxyadenosine and its a anomer from non-carbohydrate building blocks is achieved in 7 steps. The sequence builds the basic structures using bis(methylthio)methane and methylthiomethyl phenyl sulfone as both nucleophilic and electrophilic building blocks, a feature that suggests their behavior as chemical chameleons. The asymmetric induction is achieved utilizing a kinetic resolution based upon catalytic asymmetric epoxidation.

    View details for Web of Science ID A1990DQ95500002

    View details for PubMedID 2224884

  • COMPUTATIONAL MODELING OF STEREOSELECTIVITY IN THE DIELS-ALDER REACTIONS OF DIENOL ESTERS OF O-METHYLMANDELIC ACID AND THE QUESTION OF PI-STACKING JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Tucker, J. A., Houk, K. N., Trost, B. M. 1990; 112 (14): 5465-5471
  • PALLADIUM-CATALYZED CYCLOISOMERIZATIONS OF ENYNES AND RELATED REACTIONS ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M. 1990; 23 (2): 34-42
  • PALLADIUM-CATALYZED TRIMETHYLENEMETHANE REACTION TO FORM METHYLENETETRAHYDROFURANS - REACTIONS OF SUBSTITUTED TMM PRECURSORS AND MECHANISTIC INTERPRETATION JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., King, S. A. 1990; 112 (1): 408-422
  • REGIOSELECTIVE CYCLOPROPANATION VIA UNSYMMETRICAL OXATRIMETHYLENEMETHANE PALLADIUM INTERMEDIATES TETRAHEDRON LETTERS Trost, B. M., Urabe, H. 1990; 31 (5): 615-618
  • A STEREOCONTROLLED CYCLOPENTENONE SYNTHESIS VIA CYCLO-ADDITION JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Seoane, P., Mignani, S., Acemoglu, M. 1989; 111 (19): 7487-7500
  • CYCLIZATIONS VIA PALLADIUM-CATALYZED ALLYLIC ALKYLATIONS ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trost, B. M. 1989; 28 (9): 1173-1192
  • PALLADIUM-CATALYZED TRIMETHYLENEMETHANE REACTION TO FORM METHYLENETETRAHYDROFURANS - ALDEHYDE AND KETONE SUBSTRATES AND THE TIN EFFECT JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., King, S. A., Schmidt, T. 1989; 111 (15): 5902-5915
  • ON AN (OXATRIMETHYLENEMETHANE)PALLADIUM(0) COMPLEX - AN UNUSUAL PALLADIUM(0)-CATALYZED CYCLOPROPANATION JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Trost, B. M., Schneider, S. 1989; 111 (12): 4430-4433
  • SYNTHESIS OF 4-(DIMETHYLPHENYLSILYL)BUTA-2,3-DIEN-1-OL AND ITS USE IN ALKYLATION JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Tour, J. M. 1989; 54 (2): 484-486
  • A CYCLO-ADDITION STRATEGY DIRECTED TOWARD THE SPIRO RING-SYSTEM OF THE GINKGOLIDES TETRAHEDRON LETTERS Trost, B. M., Acemoglu, M. 1989; 30 (12): 1495-1498
  • AN UNUSUAL STEREOCHEMICAL DIRECTING EFFECT OF PROPARGYLIC OXYGEN SUBSTITUENTS ON AN INTRAMOLECULAR DIELS-ALDER REACTION TETRAHEDRON LETTERS Trost, B. M., HOLCOMB, R. C. 1989; 30 (51): 7157-7160
  • A NEW PALLADIUM CATALYST FOR INTRAMOLECULAR CARBAMETALATIONS OF ENYNES TETRAHEDRON LETTERS Trost, B. M., Lee, D. C., Rise, F. 1989; 30 (6): 651-654
  • ON THE MECHANISM OF PD(O) CATALYZED FORMATION OF OXAZOLIDIN-2-ONES FROM VINYL EPOXIDES TETRAHEDRON LETTERS Trost, B. M., Hurnaus, R. 1989; 30 (30): 3893-3896
  • A [3+2] CYCLO-ADDITION STRATEGY TO THE PHYLLANTHOCIN RING-SYSTEM HETEROCYCLES Trost, B. M., Moeller, K. D. 1989; 28 (1): 321-331
  • A CONVENIENT CHEMOSELECTIVE SEMIHYDROGENATION OF ACETYLENES USING HOMOGENEOUS CATALYSIS TETRAHEDRON LETTERS Trost, B. M., Braslau, R. 1989; 30 (35): 4657-4660
  • TRANSITION-METAL TEMPLATES AS GUIDES FOR CYCLIZATIONS PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES Trost, B. M. 1988; 326 (1592): 511-524
  • TRANSITION-METAL TEMPLATES AS GUIDES FOR CYCLO-ADDITIONS PURE AND APPLIED CHEMISTRY Trost, B. M. 1988; 60 (11): 1615-1626
  • CONVENIENT ALTERNATIVE APPROACH TO 2-(ACETOXYMETHYL)-3-(TRIMETHYLSILY)PROPENE JOURNAL OF ORGANIC CHEMISTRY Trost, B. M., Buch, M., Miller, M. L. 1988; 53 (20): 4887-4888
  • PD CATALYZED CHEMOSELECTIVE CYCLIZATION TO CYCLIC ETHERS TETRAHEDRON LETTERS Trost, B. M., Tenaglia, A. 1988; 29 (24): 2927-2930
  • STUDIES DIRECTED TOWARD TAXANES - PREPARATION OF ALPHA-KETOLS BY OXIDATIVE RING-OPENING OF EPOXIDES TETRAHEDRON LETTERS Trost, B. M., Fray, M. J. 1988; 29 (18): 2163-2166
  • A SYNTHESIS OF BETA-NECRODOL VIA A PALLADIUM CATALYZED REDUCTIVE ENYNE CYCLIZATION TETRAHEDRON LETTERS Trost, B. M., Braslau, R. 1988; 29 (11): 1231-1234
  • TIN MEDIATED PALLADIUM CATALYZED REGIOCONTROLLED ALKYLATIONS OF VINYL EPOXIDES TETRAHEDRON LETTERS Trost, B. M., Tenaglia, A. 1988; 29 (24): 2931-2934
  • NEW RULES OF SELECTIVITY - ALLYLIC ALKYLATIONS CATALYZED BY PALLADIUM ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M. 1980; 13 (11): 385-393
  • NEW ALKYLATION METHODS ACCOUNTS OF CHEMICAL RESEARCH Trost, B. M. 1974; 7 (3): 85-92