零价过渡金属催化无外加氧化剂的碳-氢键活化和脱氢偶联构建碳-杂键研究

Transition-metal-catalyzed carbon-hydrogen bond activation has been one of research focus in organic chemistry. The strategy, combining transition-metal-catalyzed carbon-hydrogen bond activation and dehydrogenative coupling, meets the requirement of atom economy and green chemistry. Carbon-heteroatom bond is a significant structural framework due to their widespread occurrence in natural products and medicinal chemistry. Accordingly, recent years have witnessed a rapid growth in the development of carbon-heteroatom bond formation. In this project, as-prepared special substrates will be applied in construction of aryl C(sp2)-X bond, benzyl C(sp3)-X bond and alkyl C(sp3)-X bond (X=N,O,S), which can afford a large library of various heteroatomic compounds for the discovery of lead compounds, and in synthesis of two bioactive compounds via transition-metal(0)-catalyzed carbon-hydrogen bond activation and dehydrogenative coupling strategy under oxidant-free conditions. Subsequently, reaction mechanisms will be investigated in details. Based on these studies, a new method for efficient and environmentally friendly synthesis of carbon-heteroatom bond will be established via transition-metal(0)-catalyzed carbon-hydrogen bond activation and dehydrogenative coupling strategy under oxidant-free conditions. At last, to develop a novel heterogeneous catalytic system, we will attempt to employ recyclable transition-metal(0) nanoparticles as the catalysts.

过渡金属催化的碳-氢键活化近年来已经成为有机化学领域的研究热点之一。将过渡金属催化的碳-氢键活化与脱氢偶联相结合的策略符合原子经济性和绿色化学的要求。碳-杂键广泛存在于天然产物、医药和农药等活性杂原子化合物中，因此碳-杂键形成反应是有机合成中一个非常重要的研究领域。本项目拟设计并合成特定结构的底物，采用零价过渡金属催化无外加氧化剂的碳-氢键活化和脱氢偶联策略构建芳基C(sp2)-X、苄基C(sp3)-X、烷基C(sp3)-X（X=N,O,S）三类碳-杂键，为先导化合物的筛选提供较大容量的杂原子化合物分子库，并合成两个具有生物活性的杂原子分子；深入研究各类碳-杂键构建反应的机理，建立一种基于零价过渡金属催化无外加氧化剂的碳-氢键活化和脱氢偶联策略高效、绿色地构建碳-杂键的合成新方法；最后尝试使用可循环的零价过渡金属纳米粒子作为该类反应的催化剂，发展基于此类合成策略的新型的非均相催化体系。

杂原子化合物广泛地分布于天然产物、医药以及农药中，具有突出的化学和生物活性；同时在染料、功能材料以及日用化工品等领域也有着广泛的应用。而碳-杂键是这些化合物中必不可少的化学键，通常起着官能作用。本项目旨在发展简单、高效、实用的碳-杂构建方法。通过对影响反应的各种因素实验探索，并结合核磁共振、气-质联用、透射电镜等谱仪和计算化学对反应机理进行研究，建立（零价）过渡金属催化以及无外加催化剂下碳-杂键构建的反应模型，为更多类型的碳-杂键构建反应提供理论基础和实验依据。与传统合成方法对比，本项目发展的方法使用了更为廉价易得的底物，实验操作简易，反应条件温和，反应效率高。