Catalytic Umpolung Reactions of Imines

亚胺催化还原反应

• 批准号: 8976260
• 负责人: LI DENG
• 金额: $ 34.94万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8976260
• 关键词: Amines; Ammonium; Biological Response Modifier Therapy; Biomedical Research; Carbon; Catalysis; Cinchona Alkaloids; Development; Foundations; Funding; Goals; Health; Imines; Methods; Modification; Natural Products; Nitrogen; Pathway interactions; Pharmacologic Substance; Phase; Play; Process; Property; Public Health; Reaction; Research; Research Personnel; Role; Scheme; Series; Sodium Chloride; Structure; Therapeutic Agents; Work; base; catalyst; cost effective; deprotonation; design; insight; interest; invention; novel; novel strategies; nucleophilic addition; programs; small molecule; tool

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.

描述（由申请人提供）：氮取代的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基本重要的结构单元。基于最近的初步研究中发现的大量有前途的线索和见解，建议的研究集中在设计和发现新的活性和选择性的新型手性相转移催化剂，用于开发一系列不对称亚胺umpolung反应，以直接将前手性简单和三氟甲基化亚胺转化为相应的光学活性手性胺。与传统的亚胺作为亲电试剂的亲核加成反应相比，这些新的反应利用手性有机催化剂来活化作为亲核试剂的三氟甲基亚胺和简单亚胺，以与宽范围的亲电试剂形成C-C键，从而对映选择性地生成相应的手性胺。由于催化剂诱导的亚胺反应性极性反转，这些反应被称为催化不对称亚胺聚合反应。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聚合反应。2)3）C-C键形成催化不对称亚胺聚合反应的发展，用于手性三氟甲基胺的不对称合成。这些催化的不对称亚胺umpolung反应允许新的键断开逆合成的设计，从而提供了一个从根本上新的方法对手性氨基化合物。