机械力活化的无溶剂双芳烃交叉脱氢偶联反应及其机理研究

Recent years, more and more attentions were focused on the cross dehydrogenative coupling reactions of two arenes based on the C-H bond activation due to their increasingly important role in organic synthesis. Impressive progress has been made in the tandem direct arylation, however, there are also some problems and deficiencies, such as long reaction time towards the aromatic substrates with low activity and the difficulty to avoid using excessive aromatic substrate to improve regioselectivity. Mechanochemical reactions in a ball mill without the use of solvents in the process have more advantages such as the more activities of substrate, high selectivity and fewer byproducts. In order to improve the reactivities and regioselectivities of aromatic substrates with low activities, this project plans to study the mechanical activation methods in the cross dehydrogenative coupling reactions of two arenes via selecting suitable catalytic system and mild, safe oxidant，further establishing stable and extensive applicable system under ball milling conditions. We look upon it as a promising alternative to solve the problems of the limitations in these coupling reactions, for example, substantial excess use of aromatic substrates, low recovery rates of polar solvent, long reaction time, difficulty to reuse of catalyst etc. The implementation of the project will provide a simple, fast, green method for the cross dehydrogenative coupling of arenes and apply in the synthesis of a series of functional compounds. We believe it's in line with the direction of the development of green chemistry and bring more benefit to the organic and drug synthesis under mechanochemical conditions. We also believe it has more important theoretical significance and application prospects for the development of the methodology in organic synthesis.

基于碳氢键活化的双芳烃交叉脱氢偶联反应是近年来研究热点，在有机合成中发挥着日益重要的作用。然而在取得重要进展的同时，也存在一些问题和不足，如活性较低的芳烃底物需较长的反应时间，以及需要使用过量芳烃底物来提高选择性等。机械力促进的无溶剂反应除无需使用溶剂外，还具有底物活性高、选择性专一、副反应少等优点。本项目拟将机械力活化方式引入至双芳烃的交叉脱氢偶联反应中，选择合适的催化体系以及温和、安全的氧化剂，建立稳定、适用性广的机械球磨反应体系，来解决目前该类反应存在的使用过量底物与极性溶剂、反应时间长以及催化剂回收困难等问题，提高惰性底物的反应活性与选择性，制备一系列功能性化合物。项目的实施可提供一种简单、快速、绿色的双芳烃交叉脱氢偶联反应方式，符合绿色化学的发展方向，对于拓展机械化学技术在有机及药物合成中的应用领域，丰富和发展有机合成方法学，具有较高的理论研究意义和实用价值。

本项目针对传统的溶液反应中基于碳氢键活化的交叉脱氢偶联反应存在的底物适用范围窄、反应时间长、溶剂用量大等问题，利用机械球磨高能输入的优点，研究了几类无溶剂交叉脱氢偶联反应。首先，我们对双芳烃间通过芳烃C(sp2)-H活化的偶联反应进行了研究。遗憾的是，不管是分子内还是分子间，均只得到了与催化剂用量相当的产物；随后开展的大量探索性工作并没有获得预期的研究目标。在此基础上，接下来，我们对以氯代芳烃为底物的Suzuki偶联反应进行了研究，发现在优化的催化体系及球磨条件下，收率较现有方法有较大提高。其次，我们还对机械化学条件下进行的固态不对称A3反应、Hofmann重排反应、Beckmann重排反应等进行了较为深入的研究，有效拓宽机械化学技术的应用范围，为固态化学反应机理的研究以及绿色化学的发展奠定了一定的基础。相关研究结果，已发表研究论文3篇，其中SCI论文3篇；申请中国发明专利4项，获授权专利2项。培养研究生5名。