Selective C-H Bond Functionalization in Complex Organic Synthesis

描述（由申请人提供）：该项目专注于开发新的催化方法，以在具有生物学意义的复杂有机底物中选择性官能化C-H键。选择性地将预设的C-H键转化为新的C-C键的能力对有机合成的实践具有重要的影响。上一个资助期建立了一个重要和富有成效的研究项目。在此过程中，我们证明了在复杂的有机底物中可以实现选择性的C-H键激活和功能化，并且这些过程可以在过渡金属中进行催化。此外，我们的研究表明，碳-氢键转化为合成提供了令人兴奋的战略机会。下一个资助期将继续这些努力，特别强调在杂环化合物（饱和杂环和杂芳烃）的背景下开发新的碳氢到碳-碳转化。杂环是生物活性化合物中不可缺少的结构单元，包括天然产物、蛋白质配体和药物。这一领域的新合成方法对生命科学、医学和健康具有重要意义。新的化学转化不仅有助于获得具有生物学和医学意义的所需化合物，而且还塑造了分子设计的过程。具体而言，未来的项目包括饱和杂环的C-H芳化（带有新导向基团的胺的1-芳化；sp3 C-H键），配合唑杂芳烃的直接C-H芳化（sp2 C-H键）。此外，sp3碳-氢键与烯烃交叉偶联的两种新方法（饱和杂环的1-烷基化）将被探索：第一，分子间过渡金属催化的烷基化；第二，Lewis酸催化分子内环化。这些新方法不仅将影响特定靶分子的合成，而且将重塑系列化合物制备的合成策略。复杂有机合成中选择性C-H键功能化[j]

DESCRIPTION (provided by applicant): This program focuses on the development of new catalytic methods for selective functionalization of C-H bonds in complex organic substrates of biological interest. The ability to transform selectively a preset C-H bond to a new C-C bond carries significant consequences for the practice of organic synthesis. The previous funding period established a vital and productive research program. In the process, we demonstrated that selective C-H bond activation and functionalization can be achieved in complex organic substrates and that these processes can be made catalytic in the transition metal. Also, our research showed that C-H bond transformations offer exciting strategic opportunities in synthesis. The next funding period will continue these efforts with particular emphasis on the development of new C-H to C-C transformations in the context of heterocyclic compounds (both saturated heterocycles and heteroarenes). Heterocycles are indispensable structural units frequently found in biologically active compounds, including natural products, protein ligands, and pharmaceuticals. New synthetic methods in this area are of high importance to life sciences, medicine, and health. New chemical transformations not only facilitate access to desired compounds of biological and medicinal interest, but also shape the very process of molecular design. In specific terms, the future projects include C-H arylation of saturated heterocycles (1-arylation of amines equipped with a new directing group; sp3 C-H bonds), direct C-H arylation of complex azole heteroarenes (sp2 C-H bonds). Also, two new approaches to cross-coupling of sp3 C-H bonds and alkenes (1-alkylation of saturated heterocycles) will be pursued: first, the intermolecular transition metal-catalyzed alkylation; and second, Lewis acid catalyzed intramolecular cyclization. These new methods will not only impact the synthesis of specific target molecules, but also will reshape the synthetic strategies for preparation of series of compounds. Selective C-H Bond Functionalization in Complex Organic Synthesis Resubmission Renewal Application, GM 60326 New methods for the preparation of research probes, medicinal agents, and new pharmaceuticals will be developed. Such research tools will increase the rate of understanding and potential treatment of human diseases.