Carbon-Carbon Bond-Forming Reactions Via C-H Activation

描述(申请人提供)：过渡金属催化的碳-碳键的形成对于药物制剂、天然产品和材料的合成已变得极其重要。事实上，金属催化的交叉偶联反应和烯烃歧化反应现在是有机合成中使用最多的一些反应。这些转化的重要性在很大程度上是因为它们具有广泛的官能团兼容性，并结合了大量可用作起始材料的现成化合物。 金属催化的C-H键活化和碳-碳键的形成也有可能在有机合成中变得特别强大。一些C-H活化过程，特别是那些由后过渡金属催化的过程，是高度官能团相容的。此外，由于几乎每种有机化合物都含有C-H键，因此原料的可获得性是无法超越的。然而，大多数有机化合物都含有多个C-H键，因此选择性地激活C-H键对于开发有用的合成方法是必不可少的。此外，必须确定不仅能够选择性地进行C-H活化，而且能够随后形成碳-碳键的催化剂。本提案描述了为实现这些目标而设计的强大催化方法的开发和应用。建议的研究可以分为三个具体目标。 将开发三类合成方法：(1)芳香族亚胺的分子内邻位烷基化；(2)氮杂环的烷基化；(3)氮杂环的酰化。将确定每种方法的底物范围，并在适当的情况下开发对映体选择性催化方法。每种方法的重要性也将通过合成药理活性物质来证明。

DESCRIPTION (provided by applicant): Transition metal catalyzed carbon-carbon bond formation has become incredibly important for the synthesis of pharmaceutical agents, natural products and materials. Indeed, metal-catalyzed cross-coupling reactions and olefin metathesis are now some of the most heavily used reactions in organic synthesis. The importance of these transformations is in large part due to their broad functional group compatibility combined with the large and diverse array of readily available compounds that can serve as starting materials. Metal-catalyzed C-H bond activation followed by carbon-carbon bond formation also has the potential to become exceptionally powerful in organic synthesis. Several C-H activation processes, particularly those catalyzed by late transition metals, are highly functional group compatible. In addition, because virtually every organic compound contains C-H bonds, the availability of starting materials cannot be surpassed. However, the large majority of organic compounds contain multiple C-H bonds and therefore selective C-H bond activation is essential to the development of useful synthetic methods. In addition, catalysts must be identified that enable not only selective C-H activation, but also subsequent carbon-carbon bond formation. This proposal describes the development and application of powerful catalytic methods designed to achieve these goals. The proposed research can be divided into three specific aims. Three classes of synthesis methods will be developed: (1) Intramolecular ortho-alkylation of aromatic imines, (2) Alkylation of nitrogen heterocyles, (3) Acylation of nitrogen heterocycles. The substrate scope for each method will be established, and where appropriate enantioselective catalytic methods will be developed. The importance of each method will also be demonstrated by the synthesis of pharmacologically active agents.