Ni-catalyzed Heteroaryl C‒O Bond Arylation and Homocoupling via Controlled Metal−Ligand Redox Cooperativity

Aryl ethers derived from natural sources offer a sustainable alternative to traditional aryl halides in transition-metal-catalyzed cross-coupling reactions, and challenges in their selective activation have been addressed over the past 40 years. Building on these successful researches, the focus has now shifted to bioactive molecules, such as heteroaryl ethers. Here we reported a selective C–O arylation for methoxy-heteroarene and further homocoupling by Nickel catalyst. Detailed mechanistic studies showed a 2-electron pathway was involved in C–O arylation by in-situ monitoring X-ray absorption spectroscopy (XAS) and secondary kinetic isotope experiments. Metal-ligand redox cooperation between nickel center and pyridine derivatives caused a single-electron homocoupling to form bipyridine skeleton, which is proved via XAS, in-situ monitoring ESR experiments, and characterization of isolated Ni(I) intermediates. Moreover, broad substrate scope of arylpyridines and bipyridines were applied with this synthetic strategy. It also provides a mechanistic perspective for nickel-catalyzed cross coupling via metal-ligand redox cooperation.