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: 8865271
• 负责人: Laszlo Kurti
• 金额: $ 34.59万
• 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/8865271
• 关键词: Alkenes; Amination; Amines; Amino Alcohols; Antibiotics; Aziridines; Biological Factors; Catalysis; Chemicals; Chemistry; Communities; Complex; Copper; Development; Electronics; Electrons; Epoxy Compounds; Evaluation; Excision; Exhibits; Family; Goals; Imines; Laboratories; Lead; Ligands; Methods; Nitrogen; Oxidants; Performance; Pharmaceutical Chemistry; Pharmaceutical Preparations; Prize; Production; Property; Reaction; Rhodium; Route; Synthesis Chemistry; Transition Elements; alkyl group; analog; carbene; carboxylate; catalyst; computer studies; cost; design; 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）： 氮丙啶是环氧化物的三元且同样高张力的氮类似物，由于其在多种区域选择性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合成中间体。主要是 N-H，少量是 N-烷基，也出现在具有有效抗生素、免疫调节和抗癌特性的天然产物中。氮丙啶化方法依赖于取代的氮宾转移至烯烃的C=C强键或取代的卡宾转移至亚胺的C=N键，通常，结果是带有吸电子N-保护基团的氮丙啶。其去除会导致氮丙啶的破坏。此外，这些N-保护的氮宾的高反应性也会引起非生产性的烯丙基C-H胺化。该提案有两个主要目标：（a）开发未保护（即N-H，N-烷基）氮丙啶的直接、立体特异性和实用合成方法和（b）导致邻位官能化的烯烃双官能化。这些目标将在三个具体目标中发展：（1）直接催化对映选择性的开发和优化。烯烃的N-H/N-烷基氮丙啶化；（2）开发过渡金属催化的直接氢/碳/杂原子氨基烯烃双官能化，得到未保护的氨基醇、叠氮基胺以及伯胺、仲胺和叔胺(3)一族新型N-H/N-烷基转移剂（即胺化剂），这将为直接烯烃 N-H/N-烷基氮丙啶化和氢/碳/杂原子氨基烯烃双官能化提供前所未有的化学和立体选择性。