Catalytic Umpolung Reactions of Imines

描述(申请人提供)：氮取代碳立体中心广泛存在于许多生物活性小分子和药物中。因此，手性胺是合成生物活性化合物的重要组成部分。基于最近初步研究中揭示的大量有前景的线索和见解，拟议的研究重点是设计和发现具有新活性和选择性的新型手性相转移催化剂，以开发一系列不对称亚胺Upolung反应，直接将前手性简单亚胺和三氟甲基化亚胺转化为相应的光学活性手性胺。与传统的以亚胺为亲电试剂的亲核加成反应不同，这些新的反应利用手性有机催化剂激活三氟甲基亚胺和简单的亚胺作为亲核试剂与广泛的亲电试剂形成C-C键，从而对映体选择性地生成相应的手性胺。在催化剂的作用下，亚胺的反应性发生了极性反转，这些反应被称为催化不对称亚胺Upolung反应。具体目标是：1)发现和开发新型手性有机催化剂用于不对称亚胺Upolung反应；2)开发形成C-C键的催化不对称亚胺Upolung反应，用于不对称合成手性三氟甲基胺；3)开发形成C-C键的催化不对称亚胺Upolung反应，用于不对称合成手性胺。这些催化的不对称亚胺Upolung反应允许新的键断裂用于逆合成设计，从而为手性氨基化合物提供了一种全新的方法。

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.