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中至关重要。合成的发展 可以选择性转化无处不在的C – H键为光学活动的方法 在安装各种功能的同时，化合物有望改变有机的艺术和实践 综合并应导致许多新应用。在不同的方法中，非对称C – H 通过金属催化的碳/硝基插入烷基化/氨基化代表最吸引人 C – H键的对映选择性功能化的方法。这种类型的催化碳/硝基 转移过程为C – H键的功能化提供了一种直接和一般的方法 有机化合物通过立体选择性C – C/C – N键形成。它是该工具的有用工具 生物学和物理上重要的手性有机分子的设计和合成。尽管 现有催化系统已经为C – H烷基化和胺化取得了很大进展 将某些类型的重氮化合物用作碳烯源，而Ari = nts作为硝酸盐来源， 在该领域仍然存在重要挑战，以验证确定更有效的卡宾和 硝基源结合了C – H的根本新金属催化剂的开发 烷基化和胺化。 在金属自由基催化（MRC）的概念的指导下，该研究项目针对 开发用于立体选择C – H烷基化和事故反应的新催化系统。 作为稳定的金属自由基，卟啉[CO（POR）]的钴（II）络合物已被证明起作用 通过逐步自由基机制进行C – H烷基化和分析的独特类催化剂。 在具有酰胺功能的卟啉配体支持的支持下，基于CO（II）的MRC已显示为 在激活不同类别的重氮试剂和有机叠氮化物中特别有效 烷基化和分析科学家类型的C – H键，导致C – C和C – N键形成与 有效控制反应性和选择性。在此提案中，我们将重点关注钴（II）的利用 手性甲磷脂的配合物[CO（II）（POR*）]作为手性金属催化剂 对映选择性的C – H烷基化和氨基化反应，以定为光学活性的立体选择性合成 有机分子，包括生物学上重要的碳循环和N-杂环。 我们希望这些研究最终将导致基于CO（II）的新催化的发展 立体选择性C – H烷基化和胺化反应的系统通常可以应用 实用生物学上重要的天然产品和药物有趣的合成 化合物。