Cobalt Catalyzed Vinylic C H Additions Into Imines

描述（由申请人提供）：发现新的和有效的策略来构建碳-碳键和杂原子官能团的立体选择性合成是有机化学家面临的主要挑战，因为这些过程是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核心。一种有效合成有用目标分子的现代方法是利用金属催化剂，这种催化剂能够选择性地激活其他惰性的C-H键，从而在相应的碳中心发生不同的反应性。这种策略规避了传统方法的缺点，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重点是开发钴催化乙烯C-H加成反应生成亚胺。这些过程将产生碳-碳键和手性烯丙基胺产品之间的会聚，分子间反应之间的合成中间体和亲电亚胺伙伴。研究方法将涉及创新的衬底设计，采用电子调谐导向基团进行钴介导的乙烯基C-H活化。除了实现高效的C-H活化和乙烯基加成成亚胺之外，这些导向基团还将为将产物精制成有用的有机亚结构提供方便的合成处理，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是将立体选择性钴催化乙烯加成反应发展成电子激活的手性亚砜酰亚胺亲电伙伴。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学相关靶标，包括？-氨基丁酸、吡咯烷和tropane衍生物。该研究的成功实施将凸显基于钴（III）的催化是一个有前途的研究领域，它可以替代和扩展现有的依赖于昂贵的第二和第三行金属催化剂的碳氢化合物功能化技术。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带来进一步的研究方向。

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.