羧基无痕导向的芳香羧酸单官能团化和邻双官能团化反应

Selective functionalization of arenes is one of the most attractive topics for synthesizing substituted aromatic compounds. Combining the strategy of carboxyl as a traceless-directing group and our previous preliminary work, employing carboxyl-directed ortho C-H functionalization and ipso decarboxylative cross-coupling reactions, this project aims to carry out the following works using cheap, commercially available, and safe carboxylic acids as starting materials: (1) Establishing a new methodology via an ortho C-H functionalization directed by carboxyl and subsequent ipso decarboxylation for selectively one-step synthesizing meta-substituted aromatic compounds, which are much more difficult to be prepared with the traditional methods. (2) Developing one-step approaches to provide 1,2-bifunctionalization arene derivatives. These reactions selectively occur in both ortho and ipso position of carboxyl, in which one carboxyl displays two functions. The optimal reaction conditions will be explored for 2-mono- and 1,2-bifunctionalization of aromatic carboxylic acids via screening the catalyst and optimizing the reaction conditions. The generalization of the proposed routes will be evaluated. The influence of substrates and catalytic systems will be correlated with the chemoselectivity and regioselectivity of the titled reactions. The tentative mechanism of the reactions will be proposed. The achievement of this project will have both theoretical significance and important applications for the development of efficient and green routes to prepare substituted aromatic compounds with a high selectivity.

芳环选择性官能团化反应是取代芳香化合物合成研究中最具吸引力的课题之一。本项目计划以价廉易得、品种丰富的芳香羧酸为原料，利用羧基导向芳香羧酸邻位碳氢键官能团化和原位脱羧偶联等反应，在前期工作基础上，围绕芳香羧酸羧基无痕导向策略，（1）以邻或对位取代苯甲酸为原料，通过羧基导向的芳香羧酸邻位碳氢键官能团化继而脱羧，在原羧基的邻位引入官能团，建立一步选择性合成传统付-克反应难以合成的间位取代芳香化合物的新方法；（2）建立芳香羧酸羧基邻位和原位选择性一步双官能团化反应新方法，实现“一基两用”，直接合成 1,2-双官能团化的芳烃衍生物。通过系统的催化剂筛选、反应条件优化等研究，分别找出芳香羧酸单官能团化和双官能团化反应的最优条件，研究反应的普适性和底物分子结构及催化体系与反应化学选择性、区域选择性之间关系，揭示反应机理。本项目研究对发展高选择性合成取代芳烃的高效绿色方法具有重要理论意义和应用价值。

芳环选择性官能团化反应是取代芳香化合物合成研究中最具发展潜力的方向之一。本项目以价廉易得、品种丰富的芳香羧酸为原料，根据羧基无痕导向策略，建立了一步高选择性合成传统付-克反应难以合成的间位取代二苯甲酮类化合物、间位取代联苯类衍生物的新方法；探索了1,3-二酰基取代苯的一步合成新路线；并进行了必要的拓展和深入研究，实现了羧基“一基”两用；通过羧基导向的邻位碳氢键和极性双键直接加成，实现了纯水介质中邻位烷基取代芳香羧酸的绿色合成；基于交叉脱氢偶联反应，发展了羧基邻位碳氢键直接烯基化的温和新方法；利用羧基导向碳氢键官能团化的串联环化反应，获得了3-取代苯酞、(E)-3-亚基取代苯酞、含1-茚酮骨架螺环、2-取代异吲哚啉-1-酮等环状化合物的一步高效合成新路线。系统关联分析了上述反应的普适性、底物分子结构及催化体系与反应化学/区域选择性之间的关系，提出了合理的反应机理。上述成果对拓展脱羧偶联反应及羧基为导向基的绿色催化合成具有重要的理论价值和实际意义。. 项目执行的两年期内，发表基金资助SCI论文6 篇，获授权中国发明专利3 件，申请中国发明专利5 件，获2016年度陕西省科学技术奖二等奖1 项。