应用于直接C-H键卤化的双核Pd配合物催化剂设计、合成及催化活性研究

On account of the synergistic activation between the binuclear metal centers, binuclear transition metal catalysts which imitate the stucture of biological metal enzyme can be more efficiently promote many chemical processes, and even achieve a number of new reactions that could not work through a single metal catalyst. Transition metal-catalyzed direct C-H bond functionalization is currently one of the most popular approaches in modern organic synthesis. Through developing high active and selective binuclear transition metal catalysts, cooperation between two metal centers could more successfully promote the direct C-H bond functionalization. Excellent catalytic system of direct C-H bond functionalization would have wider application and benefit energy, economic and environmental. The present item contemplate designing and synthesizing the first naphthyridine-, bipyridine-, phenanthroline-, and pyridazine-based N4-binuclear Pd complex catalysts applied in direct C-H bond halogenation, which may exist excellent catalytic activity due to the structure of the five- or six-membered Pd-ring facilitating synergy between the two metal centers, then to solve the problem about the large catalyst amount and low reactive activity in current direct C-H bond halogenation systems. Constituting the relationship between the structure character and the catalytic activity and investigating the mechanism, can help us explore the rule of binuclear catalyst synergy and building highly efficient catalysts for direct C-H bond functionalization.

模仿生物体金属酶的双核过渡金属催化剂由于双核的协同活化作用，相对单金属催化可以更高效地促进反应的进行，甚至实现一些其无法完成的化学过程。过渡金属催化直接C-H键官能化是当前有机合成最热点的课题之一，利用协同效应这一特征开发高活性高选择性的双核过渡金属催化剂来成功实现直接C-H键官能化，以使之高效的应用于范围更广泛的底物，从能源、经济及环境的角度考虑，都具有重大价值与意义。申请课题首次以直接C-H键卤化为模型反应，拟设计合成新型的以萘啶、联吡啶、菲罗啉及哒嗪等为桥联单元的N4配位双核Pd配合物催化剂，由于结构中五元及六元双金属Pd环的形成便利了反应过程中双金属中心的协同活化，催化效率将得到极大提高，解决当前直接C-H键卤化反应中存在的催化剂用量大、催化活性低等问题。通过对不同结构催化剂活性进行比较及反应机理研究，揭示双核催化剂的反应机制、协同活化原理及构建高效C-H键官能化催化剂的规律。

铜催化炔烃与叠氮1,3-偶极环加成反应被称为点击化学的精髓，在药物、生物有机、材料化学等领域具有广泛的应用。本项目成功合成了一类二吡啶甲基吡唑甲胺配体的单核和双核铜配合物，发现它们是高效的叠氮与炔烃1,3-偶极环加成反应催化剂。通过催化活性对比，发现双核配合物比对应的单核配合物存在更高的催化活性，由此获得了一种合成简单、结构稳定、用量低的叠氮与炔烃1,3-偶极环加成反应双核配合物催化剂，该催化剂可能能成为该反应已有催化体系更好的替代。随后，该催化剂被成功应用于结构相对复杂的三唑化合物合成中，成功获得了一系列索拉菲尼类似物，我们并对这些化合物进行了抗肿瘤增值活性研究，由此发现了一种非常有开发潜力的新型索拉菲尼类似物，它在对人结肠癌细胞和人乳腺癌细胞的抗增值活性是阳性对照药索拉菲尼的几十倍。此外，通过研究Cu金属中心与配体的成键情况，也摸索出一条构建高效双核催化剂的规律，为今后开发可实际应用的高效催化体系打下基础。