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  • 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
  • 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

  • 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
  • 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

  • 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

  • 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
  • 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

  • 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

  • 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
  • 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
  • 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

  • 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
  • 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

  • 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

  • Fusarisetin A: scalable total synthesis and related studies CHEMICAL SCIENCE Xu, J., Caro-Diaz, E. J., Lacoske, M. H., Hung, C., Jamora, C., Theodorakis, E. A. 2012; 3 (12): 3378-3386

    Abstract

    Fusarisetin A (1) is a recently isolated natural product that displays an unprecedented chemical motif and remarkable bioactivities as a potent cancer migration inhibitor. We describe here our studies leading to an efficient and scalable total synthesis of 1. Essential to the strategy was the development of a new route for the formation of a trans-decalin moiety of this compound and the application of an oxidative radical cyclization (ORC) reaction that produces fusarisetin A (1) from equisetin (2) via a bio-inspired process. TEMPO-induced and metal/O(2)-promoted ORC reactions were evaluated. Biological screening in vitro confirms the reported potency of (+)-1. Importantly, ex vivo studies show that this compound is able to inhibit different types of cell migration. Moreover, the C(5) epimer of (+)-1 was also identified as a potent cancer migration inhibitor, while (-)-1 and 2 were found to be significantly less potent. The optimized synthesis is applicable on gram scale and provides a solid platform for analogue synthesis and methodical biological study.

    View details for DOI 10.1039/c2sc21308g

    View details for Web of Science ID 000311920500005

    View details for PubMedID 23227303