Catalytic Umpolung Reactions of Imines

Brandeis University, Waltham MA

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Abstract

DESCRIPTION (provided by applicant): 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.