基于芳基羧酸邻位脱羧的C-H官能团反应

Owing to the unparalleled merits of aryl carboxylic acids over organosilicons, organoborons and organometalics, the development of transition-metal-catalyzed decarboxylative transformations utilizing carboxylic acids as aryl nucleophiles to participate in C-C and C-X (X = heteroatom) formation reactions becomes a hot research field of synthetic organic chemistry. This project would mainly focus on exploiting novel ortho-decarboxylative C-H functionalization reactions including ortho-decarboxylative ligand directed C-H arylation reactions, ortho-decarboxylative arylation of simple arenes, ortho-decarboxylative arylation of heterocycles and ortho-decarboxylative C-X bond formation reactions. The proposal aims at understanding of the mechanism of ortho-decarboxylative reactions, the relationship between ipso-decarboxylation and ortho-decarboxylation and the factors that govern the selectivity of decarboxylation process by the combination of experiments and theory calculations. Potential applications of ortho-decarboxylative reactions will also be illustrated via the synthesis of multiple substituted arenes, natural products and bioactive molecules that are difficult to access traditionally.

发展过渡金属催化的基于芳基羧酸作为芳基化试剂来代替昂贵的芳基硅试剂、硼试剂、金属试剂参与碳-碳键、碳-杂键形成的反应无疑是对有机合成化学的发展和丰富。本项目主要研究新型的邻位脱羧C-H官能团反应，包括邻位脱羧指导基团指导的C-H芳基化反应、邻位脱羧和简单苯交叉偶联反应、邻位脱羧和杂环的偶联反应、以及邻位脱羧碳-杂键的形成反应。结合实验与理论计算深入研究邻位脱羧的反应机理以及原位、邻位脱羧之间的关系，阐明脱羧选择性的调控因素。应用邻位脱羧反应合成传统方法难以制备的多取代芳香烃，以及天然产物和生物活性分子。

羧酸是廉价易得的有机合成原料近年来得到了有机合成化学家的广泛关注。本项目主要研究脱羧反应，实现了铑/银双金属催化脱羧脱氢串联酮β芳基化反应以及钯催化脱羧炔基化反应。同时项目还探索了C-H亚硝化反应，实现了TBAI加速的C-H亚硝化反应，并详细阐明了TBAI加速原因。最后项目把这类反应拓展到了铑催化上，能很好得到区域选择性产物。目前，在该项目的资助下脱羧反应发表了ACS Catalyst、Org Lett以及Communications Chemistry总共3篇SCI论文。其中，TBAI加速的C-H亚硝化反应已经投稿到Communication Chemistry上，目前已经接收。脱羧方面的研究成果对设计新颖的邻位脱羧反应、原位脱羧反应具有重要的指导意义。TBAI加速钯催化C-H活化对钯催化C-H活化领域研究具有一定指导意义。