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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要立体选择性 C-H 烷基化和胺化的催化自由基过程手性分子在生物学和医学的发展中至关重要。允许选择性地将普遍存在的 C-H 键转化为光学活性的方法化合物，同时安装各种功能承诺，以改变有机的艺术和实践在不同的方法中，不对称 C-H 的合成应该会带来许多新的应用。通过金属催化的卡宾/氮宾插入进行烷基化/胺化是最有吸引力的之一这种类型的催化卡宾/氮宾的对映选择性官能化方法。转移过程为 C-H 键的功能化提供了直接且通用的方法它是通过立体选择性 C-C/C-N 键形成的有机化合物。生物和药学上重要的手性有机分子的设计和合成。现有催化体系在C-H烷基化和胺化方面取得了相当大的进展使用某些类型的重氮化合物作为卡宾源和ArI=NTs作为氮宾源，该领域仍然存在重要挑战，需要确定更有效的卡宾和氮烯源以及全新 C-H 金属催化剂的开发烷基化和胺化。该研究项目以金属自由基催化（MRC）概念为指导，旨在开发用于立体选择性C-H烷基化和胺化反应的新型催化系统。作为稳定的金属自由基，卟啉 [Co(Por)] 的钴 (II) 络合物已被证明具有以下功能：一类独特的催化剂，通过逐步自由基机理进行 C-H 烷基化和胺化。由带有酰胺官能团的卟啉配体支持，基于 Co(II) 的 MRC 已被证明在激活不同类别的重氮试剂和有机叠氮化物以产生自由基方面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键的形成在本提案中，我们将重点关注钴（II）的利用。手性酰胺卟啉 [Co(II)(Por*)] 配合物作为手性金属自由基催化剂以推进用于光学活性立体选择性合成的对映选择性 C-H 烷基化和胺化反应有机分子，包括生物学上重要的碳环和N-杂环。我们希望这些研究最终能够促进基于 Co(II) 的新型催化材料的开发可普遍应用的立体选择性C-H烷基化和胺化反应系统致力于生物学上重要的天然产物和药学上有趣的实际合成化合物。