Cobalt Catalyzed Vinylic C H Additions Into Imines

钴催化乙烯基CH加成到亚胺中

• 批准号: 8784393
• 负责人: Adam Benjamin Weinstein
• 金额: $ 4.99万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784393
• 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; 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; Rhodium; Sodium Chloride; Solutions; Structure; Technology; Tropanes; base; catalyst; chemical reaction; cost; design; economic cost; functional group; innovation; interest; molecular assembly/self assembly; nucleophilic addition; public health relevance; pyrrolidine

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)：发现构建碳-碳键和杂原子官能团的立体选择性合成的新的有效策略是有机化学家面临的主要挑战，因为这些过程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。一种有效合成有用目标分子的现代方法利用了金属催化剂的优势，这种催化剂能够选择性地激活原本惰性的C-H键，从而使相应的碳中心可以发生不同的反应。这种策略绕过了传统方法的缺点，传统方法依赖浪费或昂贵的官能团操作来产生活性碳中心。所附建议书中描述的研究重点是钴催化的乙烯基C-H加成反应制亚胺的发展。这些过程将通过含有烯烃的合成中间体和亲电的亚胺伙伴之间的聚合分子间反应来产生碳-碳键和手性烯丙基胺产品。研究方法将涉及创新的衬底设计，使用电子调谐的导向基团来进行钴介导的乙烯基碳-氢活化。除了实现有效的C-H活化和亚胺中的乙烯加成外，这些导向基团还将提供方便的合成手柄，用于将产品精制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β-内酰胺。该研究方法的第二个目标将是发展立体选择性钴催化的乙烯加成反应，使其成为电子激活的手性亚磺酰亚胺亲电伙伴。能够获得富含对映体的支链烯丙基胺亚结构将使反应能够应用于生物相关目标的有效合成，包括β-氨基丁酸ACI、吡咯烷和托烷衍生物。这项拟议研究的成功实施将突出基于钴(III)的催化作为一个有前途的研究领域，以确定取代和扩展依赖昂贵的第二排和第三排金属催化剂的现有C-H官能化技术的新方法。将在这一重要领域收集的信息可能会为发现和开发相关的钴催化转化提供进一步的研究方向。