Asymmetric N-H/N-alkyl olefin azirdinations and ring-opening transformations

不对称 N-H/N-烷基烯烃叠氮化和开环转化

• 批准号: 9252464
• 负责人: Laszlo Kurti
• 金额: $ 32.07万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252464
• 关键词: Alkenes; Amination; Amines; Amino Alcohols; Antibiotics; Aziridines; Catalysis; Chemicals; Chemistry; Communities; Complex; Copper; Development; Electrons; Epoxy Compounds; Evaluation; Excision; Exhibits; Family; Goals; Imines; Laboratories; Ligands; Methods; Natural Products; Nitrogen; Oxidants; Performance; Pharmaceutical Chemistry; Pharmaceutical Preparations; Prize; Production; Property; Reaction; Rhodium; Route; Synthesis Chemistry; Transition Elements; alkyl group; analog; bioactive natural products; carbene; carboxylate; catalyst; computer studies; cost; design; immunoregulation; nitrene; novel; operation; public health relevance; salen; tertiary amine

 DESCRIPTION (provided by applicant): Aziridines, the three-membered and equally highly-strained nitrogen analogues of epoxides, are important synthetic intermediates en route to structurally complex molecules due to their versatility in myriad regio- and stereoselective transformations. The aziridine structural motif, predominantly N-H and to a lesser extent N-alkyl, also appears in natural products which exhibit potent antibiotic, immunomodulatory and anticancer properties. Current direct olefin aziridination methods rely either on the transfer of substituted nitrenes to the C=C bond of olefins or the transfer of substituted carbenes to the C=N bond of imines. Normally, the result is an aziridine bearing a strongly electron-withdrawing N-protecting group whose removal can result in destruction of the aziridine. In addition, the high reactivity of these N-protected nitrenes can give rise to non-productive allylic C-H amination as well as the loss of stereospecificity. This proposal has two main goals: (a) the development of direct, stereospecific and practical syntheses of unprotected (i.e., N-H, N-alkyl) aziridines and (b) bis-functionalization of olefins leading to vicinally functionalized amines using homogeneous transition metal catalysis. These objectives will be developed in three specific aims: (1) Development and optimization of the direct, catalytic enantioselective N-H/N-alkyl aziridination of olefins; (2) Development of transition-metal-catalyzed direct hydro-/carbo-/heteroatom-amino olefin difunctionalizations, affording unprotected amino-alcohols, azido-amines as well as primary, secondary and tertiary amines; (3) Design and synthesis of a family of novel N-H/N-alkyl transfer agents (i.e., aminating agents) that will provide an unprecedented range of chemo- and stereo-selectivities in both direct olefin N-H/N-alkyl aziridinations and hydro-/carbo-/heteroatom-amino olefin difunctionalizations.

 描述（由适用提供）：Ziridines，环氧化物的三元和同样受损坏的氮类似物，是重要的合成中间体，在结构上复杂的分子途中，由于它们在各种区域和立体式转换中的多功能性。 The aziridine structural motif, predominantly N-H and to a lesser extent N-alkyl, also appears in natural products which exposed potent antibiotic, immunomodulatory and Current direct olefin aziridination methods rely either on the transfer of substituted nitrenes to the C=C bond of olefins or the transfer of substituted carbones to the C=N bond of imines.通常，结果是一个载氮胺，具有强烈的电子，带有绘图n保护基团，其去除可能会导致副氨酸的破坏。另外，这些受N保护的硝酸盐的高反应性会导致非生产性烯丙基C-H氨基化以及静关化的丧失。该提案有两个主要目标：（a）开发直接，立体特异性和实用的合成（即N-H，N-烷基）氮杂胺，以及（b）烯烃官能化的双官能化，从而导致浪漫官能化的胺使用均匀的胺化金属催化剂。这些目标将以三个特定的目的开发：（1）烯烃的直接催化对映选择性N-H/N-烷基氮杂化的开发和优化； （2）开发过渡金属催化的直接氢 - /碳/碳 - /杂种 - 氨基烯丙基烯烃可进行的，可提供未受保护的氨基醇，氮杂氨基，偶氮胺以及原发性，中等，中等和第三级胺； （3）设计和合成新型N-H/N烷基转移剂（即修正代理），这些家族将在直接烯烃N-H/N-H/N-H烷基偶氮纤维中提供前所未有的化学和立体观念范围。