Stereoselective Radical Processes for C-H Alkylation and Amination

C-H 烷基化和胺化的立体选择性自由基过程

• 批准号: 10357917
• 负责人: X. Peter ZHANG
• 金额: $ 39.13万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10357917
• 关键词: Address; Alkylation; Amides; Amination; Arts; Azides; Benign; Biological; Biology; Carbon; Catalysis; Cobalt; Complex; Development; Electrons; Exhibits; Goals; Grant; Hydrogen Bonding; Isomerism; Lead; Ligands; Medicine; Metals; Methodology; Methods; Natural Products; Nature; Optics; Organic Synthesis; Pharmacologic Substance; Porphyrins; Process; Reaction; Reagent; Research; Research Project Grants; Source; Structure; System; Temperature; Transition Elements; base; carbene; catalyst; chemical reaction; chiral molecule; cost effective; cyclic compound; design; diazo compound; nitrene; small molecule; tool

Modified Project Summary/Abstract Section Chiral molecules are of central importance in biology and medicine. The development of synthetic methodologies that allow for selective conversion of omnipresent C–H bonds into optically active compounds while installing various functionalities promises to transform the art and practice of organic synthesis and should lead to many new applications. Among different approaches, asymmetric C–H alkylation/amination via metal-catalyzed carbene/nitrene insertion represents one of the most attractive methods for enantioselective functionalization of C–H bonds. This type of catalytic carbene/nitrene transfer process provides a direct and general approach for the functionalization of C–H bonds in organic compounds through stereoselective C–C/C–N bond formation. It serves as a useful tool for the design and synthesis of biologically and pharmaceutically important chiral organic molecules. While considerable progress has been made for C–H alkylation and amination by existing catalytic systems with the use of certain type of diazo compounds as carbene sources and ArI=NTs as nitrene sources, important challenges remain in the field that validate the need to identify more effective carbene and nitrene sources in conjunction with the development of fundamentally new metal catalysts for C–H alkylation and amination. Guided by the concept of metalloradical catalysis (MRC), this research project is directed toward the development of new catalytic systems for stereoselective C–H alkylation and amination reactions. As stable metalloradicals, cobalt(II) complexes of porphyrins [Co(Por)] have been shown to function as a unique class of catalysts for C–H alkylation and amination through stepwise radical mechanism. Supported by porphyrin ligands bearing amide functionalities, the Co(II)-based MRC has been shown to be particularly effective in activating different classes of diazo reagents and organic azides for radical alkylation and amination of diverse types of C–H bonds, leading to C–C and C–N bond formation with effective control of reactivity and selectivity. In this proposal, we will focus on the utilization of cobalt(II) complexes of chiral amidoporphyrins [Co(II)(Por*)] as chiral metalloradical catalysts to advance enantioselective C–H alkylation and amination reactions for stereoselective synthesis of optically active organic molecules, including biologically important carbocycles and N-heterocycles. We hope these studies will ultimately lead to the development of Co(II)-based new catalytic systems for stereoselective C–H alkylation and amination reactions that can be generally applied toward practical synthesis of biologically important natural products and pharmaceutically interesting compounds.

修改项目摘要/摘要部分 手性分子在生物学和医学中具有核心重要性。发展的合成方法，允许选择性转化无所不在的C-H键成光学活性化合物，同时安装各种功能有望改变艺术和实践的有机合成，并应导致许多新的应用。在不同的方法中，通过金属催化的卡宾/氮烯插入的不对称C-H烷基化/胺化是C-H键的对映选择性官能化的最有吸引力的方法之一。这种类型的催化碳烯/氮烯转移过程提供了一种直接和通用的方法，通过立体选择性C-C/C-N键的形成，在有机化合物中的C-H键的官能化。它是设计和合成生物学和药学上重要的手性有机分子的有用工具。虽然通过使用某些类型的重氮化合物作为卡宾源和ArI= NT作为氮宾源的现有催化体系，已经在C-H烷基化和胺化方面取得了相当大的进展，但是在该领域中仍然存在重要的挑战，这些挑战证实了需要鉴定更有效的卡宾和氮宾源，以及开发用于C-H烷基化和胺化的基本上新的金属催化剂。 在金属自由基催化（MRC）概念的指导下，本研究项目致力于开发立体选择性C-H烷基化和胺化反应的新催化体系。卟啉钴配合物[Co（Por）]作为稳定的金属自由基，通过逐步自由基反应机理，被证明是一类独特的C-H烷基化和胺化催化剂。在带有酰胺官能团的卟啉配体的支持下，基于Co（II）的MRC已被证明在活化不同种类的重氮试剂和有机叠氮化物以进行各种类型的C-H键的自由基烷基化和胺化方面特别有效，从而导致C-C和C-N键的形成，并有效控制反应性和选择性。在本论文中，我们将重点研究手性氨基卟啉钴配合物[Co（II）（Por*）]作为手性金属自由基催化剂，在手性C-H烷基化和胺化反应中的应用。 我们希望这些研究将最终导致钴（II）为基础的立体选择性C-H烷基化和胺化反应，可以普遍适用于对生物学上重要的天然产物和药学上感兴趣的化合物的实际合成的新的催化体系的发展。