Barry Trost, Doctoral Dissertation Advisor (AC)
Efficient Access to Chiral Trisubstituted Aziridines via Catalytic Enantioselective Aza-Darzens Reactions.
Angewandte Chemie (International ed. in English)
2017; 56 (9): 2440-2444
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 2016; 138 (11): 3659-3662
- Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral beta-Fluoroamines ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2016; 55 (2): 781-784
- Broad Spectrum Enolate Equivalent for Catalytic Chemo-, Diastereo-, and Enantioselective Addition to N-Boc Imines JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2015; 137 (50): 15940-15946
Development of Non-C2-symmetric ProPhenol Ligands. The Asymmetric Vinylation of N-Boc Imines
2015; 17 (15): 3778-3781
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
Fusarisetin A: scalable total synthesis and related studies
2012; 3 (12): 3378-3386
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