Photo-Initiated Nickel Catalysis (PiNiC): Unmasking Dimethylnickel with Light

Nickel catalysis has garnered interest in mainstream organic synthesis for constructing chemical bonds and has been merged with photoredox catalysis and electrocatalysis. Despite its success and increasing adoption by academia and industry, the mechanism by which Ni catalyzes C-C cross-coupling reactions and how the precatalyst is activated remains unclear. An exploration of stabilized dimethylNiII complexes, [(dtbbpy)Ni-(Me)2] (dtbbpy = 4,4 '-di-tert-butyl-2,2 '-bipyridine, 1) and [(bpy)-Ni(Me)2] (bpy = 2,2 '-bipyridine, 2), as Ni-precatalysts for promoting Csp2-Csp3 cross-coupling revealed that they readily undergo photo-induced Ni-C bond homolysis upon exposure to visible light and are a source of Ni0 species. Photo-initiation of dimethylNiII complexes 1 and 2 produced active Ni0 and reactive methyl radicals, which were harnessed to promote methylative and other Csp2-Csp3 cross-coupling reactions. The mechanistic studies conducted to illuminate aspects of the process include a competition reaction, NiIIArBr-complex synthesis, light-on and light -off studies, density functional theory (DFT) calculations of the bond dissociation free energies (BDFE), as well as control experiments with a Ni0-precursor. We further demonstrated the robustness and utility of dimethylNiII as a Ni0-precursor in the late -stage installation of methyl, CD3, alkyl, and benzyl groups on aryl bromides that have potential value in drug design and optimization. This work sheds light on the activation mechanism of Ni-catalyzed cross-coupling of aryl halides with organozinc reagents when a NiII-precatalyst is employed and the critical role that visible light plays in the process.