Selective C-H Bond Functionalization in Complex Organic Synthesis

描述(由申请者提供)：该计划专注于开发具有生物意义的复杂有机底物中C-H键选择性官能化的新催化方法。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意义。上一个资助期建立了一个重要而富有成效的研究计划。在这个过程中，我们证明了在复杂的有机底物中可以实现选择性的C-H键活化和功能化，并且这些过程可以在过渡金属中被催化。此外，我们的研究表明，C-H键的转换在合成中提供了令人兴奋的战略机会。下一个供资期间将继续这些努力，特别强调在杂环化合物(包括饱和杂环和杂芳烃)的背景下开发新的C-H到C-C转变。杂环是生物活性化合物中不可或缺的结构单元，广泛存在于天然产物、蛋白质配体和药物中。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和医药价值的理想化合物，而且还塑造了分子设计的过程。具体地说，未来的项目包括饱和杂环的C-H芳基化(带有新的导向基团的胺的1-芳基化；sp3 C-H键)，复杂氮杂芳烃的直接C-H芳基化(sp2 C-H键)。此外，还将寻求两种新的SP3C-H键和烯烃(饱和杂环的1-烷基化)的交叉偶联方法：第一，分子间过渡金属催化的烷基化；第二，Lewis酸催化的分子内环化。这些新方法不仅将影响特定目标分子的合成，还将重塑系列化合物的合成策略。C-H键选择性官能化在复杂有机合成再提交续期应用中的应用，GM 60326 开发研究探针、药剂和新药的新制备方法。这样的研究工具将提高对人类疾病的理解和潜在治疗的速度。

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.