银催化的通过C-H官能化构筑C-C/C-N键的反应研究

The project is focus on the development of silver-catalyzed C-C/C-N bond formation reaction via C-H functionalization on the basis of the exploration of efficient catalytic system. Based on reaction mechanisms, selection of catalytic system and design of reaction substrate, we explore intramolecular/intermolecular C-C bond formation through C-H functionalization in order to study characteristic by removing leaving groups with the generation of free radicals by the assistance of silver. We explore intramolecular/intermolecular C-N bond formation reaction via C-H functionalization with the application of free radicals in situ generated by silver mediated imino iodide(III), which could selectively react with sp3 C-H bond. Our research will organically combine silver catalysis with C-H functionalization through the control of reaction positions with high efficiency and regioselectivity without by-products, which could expand the pattern of silver-catalyzed reaction. This efficient and selective synthetic strategy for the synthesis of heterocyclics has potential application in the construction of heterocyclic structure. We will further study the reaction pathway of silver-catalyzed C-H functionalization with the assistance of theoretical calculation to speculate possible reaction mechanism. We will explore the catalytic activity and the control principle of regioselectivity to summarize the law to design this type of reaction. It would help us with the discovery of new-type silver-catalyzed C-C/C-N bond formation reaction via C-H functionalization, which could lay the foundation for efficient synthesis of complex organic compounds and natural products.

本项目旨在研究和发展新型银催化的通过C-H官能化构筑C-C/C-N键的反应。我们以反应作用机制，催化体系筛选和反应底物设计的研究和探索为支撑，考察通过银辅助的脱除离去基团形成自由基的特性，探索分子内/分子间通过C-H官能化构筑C-C键的反应；利用亚氨基高碘化物在银盐的作用下形成自由基并可以选择性与sp3 C-H键反应的特性，探索分子内/分子间通过C-H官能化构筑C-N键的反应；将银催化与C-H官能化有机结合，通过调控反应位点控制区域选择性，形成高效高选择性的杂环化合物合成策略，构筑特色鲜明、具有合成应用潜力的杂环结构。深入研究银催化C-H官能化的反应途径，并借助理论计算推测反应遵循的机理，对该类反应中催化剂的作用机制和区域选择控制原理进行深入探索，总结设计该类型反应的普遍性规律，从而发现银催化通过C-H官能化构筑C-C/C-N键的新方法，为复杂有机化合物分子和天然产物的高效合成打下基础。

本项目经过3年多的研究工作，系统研究了银催化/钯催化的通过C-H键（C-N键、C-S键、C-C键、C-B键）的活化构筑C-C键的一系列反应。我们考察了通过银辅助的脱除离去基团形成自由基的特性，通过调控反应位点控制区域选择性，形成高效高选择性的炔酮、芴酮、二芳基酮和黄酮化合物合成策略，丰富了银催化的脱羧性反应的类型，较圆满的完成了项目的计划内容。发表论文10篇(SCI收录论文9篇,其中影响因子大于3的论文6篇)，申请专利3项。项目的主要创新点体现在以下几个方面：1）银催化的芳基丙炔酸和芳基甲酰甲酸的双脱羧性自由基炔基化/环化: 温和条件下生成炔酮和黄酮化合物。2）银催化的芳基甲酰甲酸与芳基硼酸通过分子间脱羧和脱硼合成二芳基酮和银催化“一锅法”脱羧性C-H活化/环化构筑芴酮结构。3）钯催化的芳香肼/芳基磺酰肼与腈类化合物通过脱氮性加成合成芳香酮。4）芳基亚磺酸钠基于脱硫性偶联和芳基肼基于脱氮性的偶联的Suzuki类型反应。5）钯催化的吲哚嗪类衍生物的C-3位选择性C-H活化反应，分别与芳基磺酰肼通过脱氮性和脱硫性C-H直接芳基化反应，和芳基亚磺酸钠通过脱硫性C-H直接芳基化反应。项目经费使用合理，各成员齐心协力，业务水平提高明显。