镍催化碳-氧键活化烯（炔）烃的还原氢芳化反应研究

Transition-metal-catalyzed carbon-carbon bond formation reactions provide the most basic technical support for the synthesis of natural products, research and development of medicines and pesticides, modification and improvement of functional materials. Phenolic derivatives are widely existed in nature and have gradually become excellent substitutes for aryl halides. Alkenes and alkynes are often involved synthon in organic synthesis and also abundant petroleum hydrocarbon compounds. The combination of activation of inert aryl carbon-oxygen bonds with conversion of alkenes and alkynes through transition-metal-catalyzed process has high value for organic synthesis. This project aims to establish a Nickel-catalyzed system for hydroarylation of alkene and alkyne through carbon-oxygen bond activation, followed by the optimization of reaction conditions and exploration of substrate scope. This reaction could construct carbon-carbon bonds with phenol derivatives and alkenes or alkynes. In this project, we will control the regioselectivity as well as stereochemical selectivity by using ligand effect, solvent effect and other factors, and many kinds of framework structure of products could be obtained. The modification of complex molecules containing aryl carbon-oxygen bonds or alkenyl groups and alkyne groups will be carried out and the chemical selectivity of this reaction will also be studied which could display the application of this reaction in complex systems. By using experimental methods of physical organic chemistry and density functional theory calculations, this project will elucidate some catalytic issues such as reaction mechanism, rate determining step and catalytic cycle.

过渡金属催化的碳-碳成键反应能够为天然产物全合成、医药农药研发、功能材料的改性与改进提供最为基础的技术支持。酚类衍生物因其广泛存在于自然界，而逐渐成为芳基卤化物的优秀替代品。烯烃、炔烃也是有机合成中经常涉及的合成子，是丰富的石油基碳氢化合物。过渡金属催化活化惰性的芳基碳-氧键结合烯烃、炔烃的转化，具有较高的有机化学合成价值。本项目拟通过镍催化体系的建立、反应条件的优化与底物拓展，实现碳-氧键活化烯烃、炔烃的氢芳化反应，利用酚类衍生物和烯烃、炔烃构筑碳-碳键；通过配体效应、溶剂效应等因素控制反应的区域选择性、立体化学选择性，得到多种骨架结构的产物；对含芳基碳-氧键或烯基、炔基官能团的复杂分子实现转化修饰，并研究反应的化学选择性，展示反应在复杂体系中的应用；通过物理有机化学的实验手段和密度泛函理论计算的研究方法，阐明反应的机理历程、决速步骤、催化循环等问题。

过渡金属催化惰性键活化结合烯烃、炔烃转化，具有较高的有机化学合成价值。本项目发展烯烃还原偶联方法构建饱和碳-碳键，主要研究内容及取得的重要结果包括：（1）发展了镍催化惰性碳-氟键脱氟烷基化反应；（2）开发了镍催化烯烃还原烷基化制取含膦、硫精细化学品合成新路线；（3）利用串联催化、接力催化、碳-氧自由基均裂等新反应模式开发系列烷基硼酯高效合成新方法。新反应具有优良的区域和立体选择性控制，有效应用于修饰改性含烯基、碳-氧键的天然产物或药物分子。.在本项目资助下，项目负责人以第一作者或共同通讯作者身份在J. Am. Chem. Soc.（2篇）、Chem. Sci.（2篇）、Sci. China Chem.、Org. Lett.等国内外主流刊物发表论文9篇，申请中国发明专利2项。项目资助期间，项目负责人获安徽省自然科学一等奖（排名第2），入选首批“中国科学院特别研究助理资助”项目。.项目研究内容过渡金属催化的碳-碳成键反应有望为医药农药研发提供最为基础的技术支持。