The Institute for Advanced Studies, Wuhan University, Wuhan 430072, P. R. China.
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
J Am Chem Soc. 2022 Jul 6;144(26):11626-11637. doi: 10.1021/jacs.2c02487. Epub 2022 May 23.
Skeletal rearrangement that changes the connectivity of the molecule via cleavage and reorganization of carbon-carbon bonds is a fundamental and powerful strategy in complex molecular assembly. Because of the lack of effective methods to control the migratory tendency of different groups, achieving switchable selectivity in skeletal rearrangement has been a long-standing quest. Metal-based dyotropic rearrangement provides a unique opportunity to address this challenge. However, switchable dyotropic rearrangement remains unexplored. Herein, we show that such a problem could be solved by modifying the ligands on the metal catalyst and changing the oxidation states of the metal to control the migratory aptitude of different groups, thereby providing a ligand-controlled, switchable skeletal rearrangement strategy. Experimental and density functional theory calculation studies prove this rational design. The rearrangement occurs only when the nickel(II) intermediate is reduced to a more nucleophilic nickel(I) species, and the sterically hindered PDI ligand facilitates 1,2-aryl/Ni dyotropic rearrangement, while the terpyridine ligand promotes 1,2-acyl/Ni dyotropic rearrangement. This method allows site-selective activation and reorganization of C-C bonds and has been applied for the divergent synthesis of four medicinally relevant fluorine-containing scaffolds from the same starting material.
骨架重排通过碳-碳键的断裂和重组改变分子的连接性，是复杂分子组装的一种基本而强大的策略。由于缺乏有效方法来控制不同基团的迁移趋势，因此实现骨架重排的可切换选择性一直是一个长期存在的问题。基于金属的双稠合重排提供了一个解决这一挑战的独特机会。然而，可切换的双稠合重排仍未被探索。在此，我们展示了通过修饰金属催化剂上的配体并改变金属的氧化态来控制不同基团的迁移率，可以解决这个问题，从而提供了一种配体控制的、可切换的骨架重排策略。实验和密度泛函理论计算研究证明了这一合理设计。只有当镍（II）中间体还原为更亲核的镍（I）物种时，重排才会发生，而空间位阻较大的 PDI 配体有利于 1,2-芳基/Ni 双稠合重排，而三吡啶配体则有利于 1,2-酰基/Ni 双稠合重排。该方法允许对 C-C 键进行选择性激活和重组，并已应用于从同一起始原料出发，对四个具有药用相关性的含氟支架进行发散合成。
