钯催化下降冰片烯介导的烯胺选择性碳-氢键官能团化反应研究

In recent years, palladium catalyzed C-H bond functionalization has become one of the most important and vibrant areas of organic chemistry research, gradually showing the advantage in reaction mode and efficiency over traditional methods. However, most Pd-catalyzed C-H bond functionalization of enamines was found to be limited to the transformation of β C-H bonds to C-C bonds. To solve these problems, this project will focus on the study of Pd-catalyzed α functionalization of enamines via norbornene-mediated C-H activation. With cyclic enamines as substrates, the palladium-catalyzed norbornene-mediated C-H bond functionalization will first be investigated to introduce new carbon-carbon and carbon-heteroatom bonds at the α position of enamines. Then, the substrate scope will be expanded to allow for straightforward and regioselective α functionalization of non-cyclic enamines. Application of this methodology in the synthesis of bio-active molecules will also be demonstrated. Based on detailed discussion on the reaction mechanism, the interaction among various components involved in the reaction will be disclosed. With this research project, a novel and efficient route for the regioselective α C-H bond functionalization of enamines should be developed. The results and development obtained from this project will enrich approaches to the synthesis of complex organic targets.

钯催化的C-H键官能团化反应由于其新颖的反应模式和良好的原子经济性，已成为有机化学研究的热点领域。目前钯催化的烯胺类化合物的C-H键官能团化反应局限于底物β位碳碳键的引入。针对此问题，项目提出利用Pd催化下的降冰片烯介导机制来实现烯胺类化合物α位C-H键官能团化的新思路，将详细研究环状烯胺类底物α位C-H键的高效高选择性活化，构建碳碳键、碳杂键等多种类型的化学键；拓宽反应的适用范围至开链的烯胺类化合物，并将此方法应用于生物活性分子的合成中；通过深入研究反应过程与机理，阐明烯胺α位C-H键官能团化反应机制，揭示各反应因素之间的关系和规律性。研究成果对于丰富C-H键官能团化理论，高选择性地构建多种有机合成砌块及生物活性分子具有重要的科学意义。

过渡金属钯催化的C-H键官能团化反应是有机合成研究的热点领域之一，具有原子经济性高、催化效率好、普适性广、应用性强等特点。项目对烯胺化合物在钯存在下的选择性C-H键官能团化的反应进行了尝试。探索了Pd催化下基于4-喹啉酮类烯胺化合物与醋酸碘苯所得高价碘叶立德中间体重排产物的C-H键活化反应，高效高选择性地构建多并环结构：从易得的碘苯类化合物出发，通过原位氧化得到的三价碘物种对惰性芳烃化合物氧化得到碘叶立德中间体，中间体快速重排为碘代芳烃，再结合过渡金属钯催化的C(sp2)-H键活化环化得到二芳基并呋喃环产物。以及直接利用带烷基的三价碘试剂，结合过渡金属钯催化的C(sp3)-H键芳基化反应在非活化的烷基基团上有效引入芳基，快速构建二芳基并吡喃化合物；项目还发展了路易斯酸Bi(OTf)3催化的C(sp3)-H键活化反应实现了含有全碳季碳手性中心的氧化吲哚骨架的合成；此外，也研究了过渡金属钯催化的自由基环化反应，实现非活化烯烃的氟烷基芳基化反应，以及氮杂环卡宾催化的不饱和羰基化合物的芳基化反应；最后在催化剂负载基体的设计制备方面开展了一些工作，如具有自愈合性能和pH响应性能的纤维素/聚乙烯醇水凝胶基体的制备，化学及物理改性纤维素小球的制备，并对它们的性能进行了研究。