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(由申请人提供)：氮杂环丙烷是环氧化物的三元氮类似物，也是高度应变的氮类似物，由于其在无数区域和立体选择性转化中的多功能性，是合成结构复杂分子的重要中间体。氮杂环丙烷的结构基序，主要是N-H，少量N-烷基，也存在于天然产物中，表现出强大的抗菌、免疫调节和抗癌特性。目前的直接烯烃氮杂化方法要么依赖于取代的硝烯转移到烯烃的C=C键，要么依赖于取代卡宾转移到亚胺的C=N键。正常情况下，结果是氮杂环丙烷带有强吸电子的N-保护基团，其移除会导致氮杂环丙烷的破坏。此外，这些N-保护的硝烯的高反应性可能导致非生产性的烯丙基C-H胺化以及立体专一性的丧失。这项建议有两个主要目标：(A)开发无保护(即N-H，N-烷基)氮杂环丙烷的直接、立体专一性和实用性合成；(B)利用均相过渡金属催化使烯烃双官能化得到邻位官能化的胺。开发这些目标的具体目标有三个：(1)开发和优化直接催化的N-H/N-烷基氮烷基叠氮化反应；(2)开发过渡金属催化的直接氢化/碳/杂原子-氨基烯烃官能化反应，得到无保护的氨基醇、叠氮胺以及伯胺、仲胺和叔胺；(3)设计和合成了一系列新型的N-H/N-烷基转移剂(即胺化试剂)，它们将在N-H/N-烷基氮化和氢/碳/杂原子-氨基双官能化反应中提供前所未有的化学和立体选择性。