基于脱羧的芳香化合物的C-H键芳基化

Our research will focus on the newly developed decarboxylative C-H bond arylation reactions. The two main aims of the project are: 1) to develop the method of decarboxylative C-H bond arylation of arenes with benzoic acids that lacking of o-substituted group. The major challenge of the reaction is the decarboxylation of the benzoic acids lacking of o-substituted group under the normal decarboxylation conditions. To deal with the problem, we'll try to synthesize some ligands to improve the decarboxylative activity of the catalyst by controlling the steric and electronic effect of the metal center. 2) Using oxygen or other cheap and environmental friendly oxidants to improve the decarboxylative C-H bond arylation of arenes with o-substituted benzoic acids or heteroaryl carboxylic acids. A totally new catalytic system is required to develop the method because of kinds of limitations of the old decarboxylative catalytic systems. A way to solve the problem is to introduce ligand such as N-Heterocyclic Carbene that won't be oxidized by the oxidant to the reaction system, improving the decarboxylative activity of the catalyst by controlling the steric and electronic effect. Besides, the matching of the rate of decarboxylation step and C-H bond activation step is also required. We'll control the rates by adjusting the effects of solvents, ligands, temperature and other factors.

我们的研究将主要集中于基于脱羧的C-H键芳基化反应。本项目的两个关键目标为：1）发展芳基化合物与非邻位取代苯甲酸化合物的脱羧/C-H键芳基化反应。反应的主要难点在于在现有的普通的脱羧条件下对非邻位取代羧酸进行脱羧。为了解决这个问题，我们将合成一系列配体，通过控制催化剂中心金属的立体因素和电子因素来促进催化剂的脱羧反应活性。2）使用氧气等廉价、环境友好的氧化剂来促进芳基化合物与邻位取代苯甲酸及杂环羧酸的脱羧/C-H键芳基化反应。由于旧有脱羧催化体系不能很好的容忍这样的氧化体系，具有各种限制，我们需要发展一种全新的催化体系。我们拟引入一些类似于氮卡宾这样的不会被这些氧化剂氧化的配体，通过调节催化剂位阻和电子效应来达到研究目的。此外，脱羧步骤和C-H活化步骤的速率匹配对于反应的成功也至关重要，我们拟通过调控相关的溶剂、配体和反应温度等要素来实现我们的目标。

鉴于脱羧反应和C-H键官能团化各自的优势，脱羧与C-H键官能团化相结合的偶联反应无疑具有重要科学意义和研究价值。在我们最近发现的基于C-H键活化和脱羧过程新反应的基础上，拟通过深入研究芳基羧酸脱羧偶联的反应特性和芳香化合物C-H键活化偶联的反应特性，认识它们的共通兼容之处，从而构建全新的交叉偶联反应。本项目在实施期间，圆满完成了项目计划书预期的要求，主要发展了基于芳基羧酸脱羧呋喃等杂环的C-H键直接官能团化反应、羧酸基做“无痕”指导基团的芳基羧酸与噻吩的氧化脱氢/脱羧串联反应等高效简洁的催化体系，在Angew Chem. Int. Ed., Org. Lett. 等国际著名期刊杂志发表论文5篇，综述论文1篇。