Recent development of Ni-catalyzed C-H activation

In recent years, progress in synthetic organic chemistry has been propelled by light-induced reactions, especially by combining photoredox catalysis with nickel catalysis to facilitate cross-coupling reactions that were previously unattainable. Our group embarked on exploring the activation of nickel catalysts through light over the past 5 years, aiming to develop gentle and selective C(sp3)−H cross-coupling reactions by light exposure, eliminating a Ni−Cl bond. Inspired by Nocera laboratory findings, we envisioned using light-induced chlorine atoms to facilitate hydrogen atom transfer (HAT), enabling redox-neutral processes. A Ni/photoredox-catalyzed α-oxy C(sp3)−H arylation was developed and extended it to selectively functionalize aryl chlorides, even those in complex substrates. Exploring various oxidation states, Trimethyl orthoformate was utilized as a methyl radical source for methylation reactions and cross-coupling with feedstock chemicals and late-stage intermediates. Mechanistic investigations, including computational simulations and spectroscopic analyses, revealed the crucial role of chlorine radical generation in these methods, emphasizing the importance of understanding the photochemical behavior of cross-coupling catalysts in metallaphotoredox processes. Deeper insights gained from these studies are expected to facilitate the design of new catalysts and the development of innovative synthetic methods.