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

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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.