过渡金属催化的不对称（杂环）芳烃碳杂（N/O）偶联反应的研究

The chiral aromatic ether, aromatic amine with an hetero-arylated moiety are prevalent in a variety of pharmaceuticals, pesticides, organic intermediate compounds and flavors. The transition-metal-catalyzed cross-coupling reactions have emerged as a powerful method to construct aryl C-C bond and C-hetero bond in organic synthesis. Although great progress has been made in transition-metal catalyzed asymmetric aryl C-C cross coupling reaction, little attention has been focused on asymmetric aryl C-heteroatom coupling reaction. This project intends to study on the Transition-Metal-Catalyzed asymmetric aryl (Heteroaryl) C-heteroatom(N/O) cross-coupling reaction with the strategies of desymmetrization, dynamic kinetic resolution and C-H activation: 1) Develop desymmetric intermolecular cross coupling reaction of alkyl halides with heteroatom-containing nucleophilic reagents; 2) Focus on developing Transition-Metal-Catalyzed enantioselective cross-coupling reactions of arenes or heteroarenes with amines or alcohols via transition-metal-catalyzed C-H activation: the direct C-H bond activation of heteroarenes which is aimed at more acidic C-H bond; the directed C-H bond activation of arenes which need a directing group to coordinate with the metal. We intends to design rational reactions and screen catalytic systems systemly, which may provide efficient routes for the synthesis of chiral aromatic ethers and amines.

含有芳香碳杂键的手性化合物在医药、农药、有机合成中间体、香料等领域具有重要的作用。过渡金属催化的交叉偶联反应是构筑芳烃碳碳键、碳杂键的有效策略，广泛应用于有机合成。目前不对称的交叉偶联反应主要集中于芳烃碳碳键偶联，而不对称的芳烃碳杂偶联研究较少。本项目拟利用不对称去对称化、动态动力学拆分、碳氢键活化的策略，开展过渡金属催化的不对称（杂环）芳烃碳杂（N/O）偶联反应：1）开发分子间的不对称卤代芳烃碳杂偶联反应；2）侧重开发基于碳氢键活化的芳烃、杂环芳烃与胺类、醇类化合物的不对称交叉偶联反应——对杂环芳烃进行直接活化，对芳烃进行导向活化。我们将对反应进行合理设计，并系统地筛选催化体系，为芳香醚、芳香胺类手性化合物提供有效的合成策略。

含杂原子的手性化合物尤其是手性杂环类化合物在医药领域发挥着重要的价值。过渡金属催化的芳烃碳氮、碳氧偶联反应是构筑芳烃碳杂键的有效策略。开发过渡金属催化的不对称芳烃碳杂偶联反应合成手性芳基醚类、芳基胺类化合物具有重要的研究意义。本项目开展了过渡金属催化的不对称芳烃碳氮、碳氧偶联反应的研究以及杂环类化合物的合成研究与生物活性研究。1）完成了铜催化的不对称芳烃碳氧偶联反应的研究，利用不对称去对称化策略，通过芳烃双碳氧偶联反应实现了含氧手性螺环化合物的不对称合成，产物获得了良好的收率与光学选择性。2）实现了铜催化的不对称分子间芳烃碳氮偶联反应的研究，以二芳基碘鎓盐与磺酰胺为底物进行不对称芳烃碳氮偶联反应，产物获得了较高的光学选择性与较高的收率。3）通过碱催化的Boulton-Katritzky重排氮氮成键环化反应构建了1,2,4三氮唑酮的研究，异噁唑类底物在碱性条件下重排环化反应，高产率便捷的合成了系列三氮唑酮类化合物。4）基于本项目的资助开展了相关应用研究，对获得的化合物进行了抗病毒活性测试研究。