Nitrogen-substituted carbon stereocenters are widely presented in numerous biologically active small molecules and pharmaceuticals. Thus, chiral amines are fundamentally important building blocks for the synthesis of biologically active compounds. Building on a wealth of promising leads and insights revealed in recent preliminary studies, the proposed studies focus on the design and discovery of novel chiral phase transfer catalysts of new activity and selectivity for the development of a series of asymmetric imine umpolung reactions to directly transform prochiral simple and trifluoromethylated imines into the corresponding optically active chiral amines. In contrast to conventional nucleophilic addition reactions where imines serve as an electrophile, these new reactions utilize chiral organocatalysts to activate trifluoromethyl imines and simple imines as nucleophiles to form C-C bonds with a broad range of electrophile to enantioselectively generate the corresponding chiral amines. With a catalyst-induced reversal of the polarity in the reactivity of imines, these reactions are termed as catalytic asymmetric imine umpolung reactions.
The specific aims are: 1)The discovery and development of novel chiral organocatalysts for asymmetric imine umpolung reactions.; 2) The development of C-C bond forming catalytic asymmetric imine umpolung reactions for the asymmetric synthesis of chiral trifluoromethylated amines; 3) The development of C-C bond forming catalytic asymmetric imine umpolung reactions for the asymmetric synthesis of unfunctionalized chiral amines. These catalytic asymmetric imine umpolung reactions allow novel bond disconnections for retrosynthetic design and consequently provide a fundamentally new approach toward chiral amino compounds.
Small molecules constitute one of the most important forms of therapeutic agents and play an increasingly important role in both basic and translational biomedical research. The goal of this work is to develop new synthetic methods that will greatly enhance our ability to rapidly create molecules of diverse structures with defined configuration, thereby providing biomedical researchers with powerful tools for the discovery of small molecules possessing biologically interesting and therapeutically desirable properties. These synthetic methods will also provide the foundation for the development of cost-effective processes for the sustainable manufacturing of therapeutic agents with significant implications to public health.
|Lu, Xiaojie; Deng, Li (2014) Catalytic asymmetric peroxidation of ?,?-unsaturated nitroalkenes by a bifunctional organic catalyst. Org Lett 16:2358-61|
|Provencher, Brian A; Bartelson, Keith J; Liu, Yan et al. (2011) Structural study-guided development of versatile phase-transfer catalysts for asymmetric conjugate additions of cyanide. Angew Chem Int Ed Engl 50:10565-9|
|Liu, Yan; Provencher, Brian A; Bartleson, Keith J et al. (2011) Highly Enantioselective Asymmetric Darzens Reactions with a Phase Transfer Catalyst. Chem Sci 2:1301-1304|
|Wu, Yongwei; Singh, Ravi P; Deng, Li (2011) Asymmetric olefin isomerization of butenolides via proton transfer catalysis by an organic molecule. J Am Chem Soc 133:12458-61|
|Bartelson, Keith J; Singh, Ravi P; Foxman, Bruce M et al. (2011) Catalytic Asymmetric [4 + 2] Additions with Aliphatic Nitroalkenes. Chem Sci 2:1940-1944|
|Li, Hongming; Liu, Xiaofeng; Wu, Fanghui et al. (2010) Elucidation of the active conformation of cinchona alkaloid catalyst and chemical mechanism of alcoholysis of meso anhydrides. Proc Natl Acad Sci U S A 107:20625-9|
|Singh, Ravi P; Foxman, Bruce M; Deng, Li (2010) Asymmetric vinylogous aldol reaction of silyloxy furans with a chiral organic salt. J Am Chem Soc 132:9558-60|
|Liu, Yan; Sun, Bingfeng; Wang, Baomin et al. (2009) Catalytic asymmetric conjugate addition of simple alkyl thiols to alpha,beta-unsaturated N-acylated oxazolidin-2-ones with bifunctional catalysts. J Am Chem Soc 131:418-9|
|Li, Hongming; Song, Jun; Deng, Li (2009) Catalytic enantioselective conjugate additions with alpha,beta-unsaturated sulfones. Tetrahedron 65:3139-3148|
|Sun, Bing-Feng; Hong, Ran; Kang, Yan-Biao et al. (2009) Asymmetric total synthesis of (-)-plicatic acid via a highly enantioselective and diastereoselective nucleophilic epoxidation of acyclic trisubstitued olefins. J Am Chem Soc 131:10384-5|
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