氧气条件下基于DMF参与的Cu催化芳基羧酸脱羧官能团化反应研究

The introduction of functional group into the structure of small organic molecules can remarkably change their properties, including physical, chemical and biological performances. As a result, transition-metal catalyzed functionalization of small organic molecules is a hot research project in organometallic chemistry. Carboxylic acids are a kind of cheap, stable and nontoxic compounds, which deliver innocuous CO2 during decarboxylation process, thus, it's a green method to furnish other molecules via decarboxylative functionalization of carboxylic acids.. DMF is a common reagent in laboratory, which can furnish several building blocks including -NMe2 and CN synthetic units under different conditions. Unfortunately, there has been no report on decarboxylative N,N’-dimethyl amination and cyanation of aryl carboxylic acids until now. Basing on understanding of related reports and our incipient research on Cu-mediated decarboxylative functionalization of aryl carboxylic acids, this application project is a research on Cu-catalyzed decarboxylative functionalization of aryl carboxylic acids with DMF under aerobic conditions.. The research of desired reactions is involved in coordinating reaction rate of generation of Ar-Cu intermediate via decarboxylation of carboxylic acid substrate with production of functionalized reagent through the activation of DMF in the presence of several reaction parameters including Cu catalyst, ligand, additive and temperature; regenerating and recycling active catalytic particles under aerobic conditions; understanding reaction intermediates and mechanism. On the other hand, the research of desired reactions is concerned with the development of cheap and green reaction, and solution of basic organometallic reaction problems.

在有机小分子结构上引入官能团能显著改变其物理、化学和生物性质，因此，过渡金属催化有机小分子的官能团化反应是当前金属有机化学的研究热点。羧酸具廉价稳定和无毒的特点，且脱羧过程只释放出CO2，故通过羧酸的脱羧官能团化反应无疑是绿色方法。. DMF是常见的实验室试剂，能在不同条件下提供包括-NMe2、CN在内的多种合成砌块。然而，有关DMF参与的羧酸脱羧N,N’-二甲基胺化和氰化反应在目前仍是空白。基于相关报道和我们前期研究，申请项目立足于氧气条件下DMF参与的Cu催化芳基羧酸脱羧官能团化反应研究。. 目标反应涉及到协调羧酸脱羧生成Ar-Cu中间体速率与DMF被活化形成官能团化试剂速率相匹配所需的Cu催化剂、配体、添加剂、温度等参数；氧气条件下的催化剂活性粒子再生与循环；反应中间体及机制的认识。另一方面，目标反应的实现关系到廉价绿色反应的发展和基础金属有机反应问题的解决。

基于脱羧化学的绿色性与廉价性，通过利用廉价DMF为溶剂和底物，针对目标反应的研究，我们分别解决了有氧条件下基于DMF的Cu参与促进芳基羧酸脱羧的叔胺化和氰化反应，并进一步发展了以甲酰胺或N-甲基甲酰胺为伯胺源或仲胺源的脱羧胺基化反应，分别探讨了上述脱羧官能团反应的底物普适性、反应实用性与机理。在上述工作基础上，我们开展了关联化研究，相继实现了过渡金属Cu参与促进的脱羧卤化、Pd/Cu催化羧基无痕导向其邻位C-H键卤化反应、无金属条件下羧酸与溶剂CH2Cl2或DMSO的成酯反应，以及电化学条件下芳基硼酸脱硼官能团化等反应。. 项目研究过程中，在Org. Lett.、Org. Chem. Front.、Green Chem.、Chin. Chem. Lett.等国际主流化学杂志发表论文21篇；授权专利1 项；培养了具有良好科研素质的硕士研究生7名。.