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: 10796195
• 负责人: X. Peter ZHANG
• 金额: $ 16.69万
• 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/10796195
• 关键词: Alkylation; Amides; Amination; Azides; Benign; Biological; Biology; Catalysis; Cobalt; Complex; Development; Environment; Exhibits; Hydrogen Bonding; Isomerism; Ligands; Medicine; Metals; Methodology; Methods; Natural Products; Optics; Organic Synthesis; Porphyrins; Process; Reaction; Reagent; Research Project Grants; Source; System; Transition Elements; carbene; catalyst; chemical reaction; chiral molecule; cost effective; design; diazo compound; enantiomer; nitrene; tool

PROJECT SUMMARY/ABSTRACT Catalytic Radical Processes for Stereoselective C–H Alkylation and Amination 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.

项目摘要/摘要 立体选择性C-H烷基化和胺化反应的催化自由基反应 手性分子在生物学和医学中具有重要意义。合成纤维的研究进展 允许将无处不在的C-H键选择性地转化为光学活性的方法 化合物，同时安装各种功能，承诺改变有机的艺术和实践 合成，并将导致许多新的应用。在不同的方法中，不对称C-H 通过金属催化的卡宾/硝烯插入的烷基化/胺化反应是最具吸引力的方法之一 C-H键的对映选择性功能化方法。这类催化的卡宾/硝烯 转移过程为C-H键的官能化提供了一种直接和通用的方法 有机化合物通过立体选择性的C-C/C-N键形成。它是一种有用的工具，可用于 设计和合成具有生物和药学意义的重要手性有机分子。而当 现有的催化体系在C-H烷基化和胺化反应中取得了很大的进展 通过使用某些类型的重氮化合物作为卡宾来源和Ari=NTS作为氮源， 在该领域仍然存在重要的挑战，证实需要确定更有效的卡宾和 氮源与C-H新型金属催化剂的开发 烷基化和胺化。 在金属催化(MRC)概念的指导下，本研究项目旨在 立体选择性C-H烷基化和胺化反应新催化体系的开发。 作为稳定的金属化合物，卟啉钴(II)络合物[Co(Por)]被证明具有如下功能 一类独特的用于C-H烷基化和胺化反应的催化剂。 在含酰胺官能团的卟啉配体的支持下，基于Co(II)的MRC被证明是 对不同类别的重氮试剂和有机叠氮类自由基的活化特别有效 不同类型的C-H键的烷基化和胺化，导致C-C和C-N键的形成 有效控制反应性和选择性。在这项提案中，我们将重点讨论钴(II)的利用 手性氨基卟啉配合物[Co(II)(Por*)]作为手性金属催化剂的进展 立体选择性合成光学活性化合物的不对称C-H烷基化和胺化反应 有机分子，包括具有生物重要性的碳环和N-杂环。 我们希望这些研究将最终导致基于Co(II)的新型催化剂的开发 可普遍应用的立体选择性C-H烷基化和胺化反应体系 走向生物重要天然产物的实用合成和药用价值 化合物。