Cobalt Catalyzed Vinylic C H Additions Into Imines

钴催化乙烯基CH加成到亚胺中

• 批准号: 9130206
• 负责人: Adam Benjamin Weinstein
• 金额: $ 2.19万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9130206
• 关键词: Agrochemicals; Alcohols; Alkenes; Amides; Amines; Amino Acids; Architecture; Area; Attention; Benign; Carbon; Catalysis; Chemicals; Cobalt; Complex; Coupling; Development; Diamines; Disadvantaged; Electrons; Employment; Generations; Goals; Halogens; Health; Hydrogen Bonding; Imines; In Situ; Lactams; Mediating; Metals; Methods; Molecular; Nitrogen; Organic Synthesis; Oximes; Oxygen; Pharmacologic Substance; Pharmacotherapy; Preparation; Process; Production; Pyrroles; Pyrrolidines; Reaction; Reagent; Research; Sodium Chloride; Structure; Technology; Tropanes; base; catalyst; chemical reaction; cost; design; economic cost; functional group; innovation; interest; molecular assembly/self assembly; novel therapeutics; nucleophilic addition

DESCRIPTION (provided by applicant): The discovery of new and efficient strategies for the construction of carbon-carbon bonds and the stereoselective synthesis of heteroatom functional groups is a primary challenge for organic chemists, as these processes are central to the ability to synthesize complex architectures prevalent in biologically active pharmaceuticals and agrochemicals. A modern approach to the efficient synthesis of useful target molecules takes advantage of metal catalysts that are capable of selective activation of an otherwise inert C-H bond, such that diverse reactivity can occur at the corresponding carbon center. This strategy circumvents the disadvantages of traditional approaches that rely on wasteful or costly functional group manipulations in order to generate reactive carbon centers. The research described in the attached proposal is focused on the development of cobalt catalyzed vinylic C-H addition reactions into imines. These processes will give rise to carbon-carbon bonds and chiral allylic amine products by convergent, intermolecular reactions between olefin-containing synthetic intermediates and electrophilic imine partners. The research approach will involve innovative substrate designs that employ electronically tuned directing groups for cobalt mediated vinylic C-H activation. In addition to enabling efficient C-H activation and vinylic addition into imines, these directing groups will provide convenient synthetic handles for the elaboration of the products into useful organic substructures, including 1,3-diamines, 1,4-diamines, 1,4-amino acids, pyrroles and ?-lactams. A second goal of the research approach will be the development of stereoselective cobalt catalyzed vinylic addition reactions into electronically activated chiral sulfinyl imine electrophilic partners. The ability to access enantioenriched branched allylic amine substructures will allow for the application of the reactions to the efficient synthesis of biologically relevant targets, including ?-aminobutyric aci, pyrrolidine, and tropane derivatives. Successful execution of the proposed research will highlight cobalt(III)-based catalysis as a promising area of study for the identification of new methods that replace and expand upon existing C-H functionalization technologies which rely on expensive second- and third-row metal catalysts. The information that will be gathered in this important area will likely spawn further research directions for the discovery and development of related cobalt catalyzed transformations.

描述（由申请人提供）：发现用于构建碳-碳键和立体选择性合成杂原子官能团的新的有效策略是有机化学家的主要挑战，因为这些方法对于合成生物活性药物和农用化学品中普遍存在的复杂结构的能力至关重要。有效合成有用的目标分子的现代方法利用能够选择性活化否则惰性的C-H键的金属催化剂，使得在相应的碳中心处可以发生不同的反应性。这种策略避免了传统方法的缺点，传统方法依赖于浪费或昂贵的官能团操作，以产生活性碳中心。所附提案中描述的研究集中于钴催化乙烯基C-H加成反应生成亚胺的发展。这些过程将产生碳-碳键和手性烯丙基胺产品之间的收敛，含烯烃的合成中间体和亲电子亚胺合作伙伴的分子间反应。研究方法将涉及创新的基板设计，采用电子调谐钴介导的乙烯基C-H活化的导向基团。除了使有效的C-H活化和乙烯基加成到亚胺中之外，这些导向基团还将提供方便的合成手柄，用于将产物加工成有用的有机亚结构，包括1，3-二胺、1，4-二胺、1，4-氨基酸、吡咯和？内酰胺。研究方法的第二个目标将是立体选择性钴催化乙烯加成反应的发展成为电子活化的手性亚磺酰亚胺亲电合作伙伴。获得对映体富集的支链烯丙基胺亚结构的能力将允许将反应应用于有效合成生物相关靶标，包括？氨基丁酸、吡咯烷和托烷衍生物。拟议研究的成功执行将突出钴（III）基催化作为一个有前途的研究领域，用于确定新方法，取代和扩展现有的C-H官能化技术，这些技术依赖于昂贵的第二和第三行金属催化剂。在这一重要领域收集的信息可能会为相关钴催化转化的发现和发展提供进一步的研究方向。