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: 10557084
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557084
• 关键词: Address; Alkylation; Amides; Amination; Azides; Benign; Biological; Biology; Carbon; Catalysis; Cobalt; Complex; Development; Electrons; Environment; Exhibits; Goals; Grant; Hydrogen Bonding; Isomerism; Ligands; Medicine; Metals; Methodology; Methods; Natural Products; Nature; Optics; Organic Synthesis; Porphyrins; Process; Reaction; Reagent; Research; Research Project Grants; Source; Structure; System; Temperature; Transition Elements; carbene; catalyst; chemical reaction; chiral molecule; cost effective; cyclic compound; design; diazo compound; enantiomer; member; 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.

修改后的项目摘要/摘要部分 手性分子在生物学和医学中具有重要意义。合成方法的发展允许将无处不在的C-H键选择性地转化为光学活性化合物，同时安装各种官能团，有望改变有机合成的艺术和实践，并将导致许多新的应用。在不同的方法中，通过金属催化的卡宾/硝基插入的不对称C-H烷基化/胺化反应是最具吸引力的C-H键对映选择性官能化方法之一。这种催化的卡宾/硝烯转移过程为通过立体选择性的C-C/C-N键的形成使有机化合物中的C-H键功能化提供了一种直接和普遍的方法。它是设计和合成具有生物和药学意义的重要手性有机分子的有用工具。虽然现有的催化体系在C-H烷基化和胺化反应中取得了相当大的进展，使用了某些类型的重氮化合物作为卡宾源，Ari=NTS作为氮源，但在该领域仍然存在重要的挑战，需要结合开发用于C-H烷基化和胺化的根本新型金属催化剂来验证寻找更有效的卡宾和氮源的必要性。 在金属催化(MRC)概念的指导下，本研究项目旨在开发用于立体选择性C-H烷基化和胺化反应的新催化体系。作为一种稳定的金属化合物，卟啉钴(Ⅱ)配合物[Co(Por)]是一类独特的C-H烷基化和胺化催化剂，其催化机理是逐步自由基反应。在含酰胺功能的卟啉配体的支持下，基于Co(II)的MRC被证明特别有效地激活了不同类型的重氮试剂和有机叠氮化合物，用于不同类型的C-H键的自由基烷基化和胺化，导致C-C和C-N键的形成，有效地控制了反应的活性和选择性。在这项建议中，我们将集中于利用手性氨基卟啉钴(II)配合物[Co(II)(Por*)]作为手性金属催化剂来推进立体选择性的C-H烷基化和胺化反应，用于立体选择性地合成光学活性有机分子，包括生物上重要的碳环和N-杂环。 我们希望这些研究将最终导致基于Co(II)的新型催化体系的开发，用于立体选择性的C-H烷基化和胺化反应，这些反应可以普遍应用于具有重要生物意义的天然产物和具有药用价值的化合物的实际合成。