Reductively Induced Aryl Transmetalation: An Alternative Catalytically Relevant Ni-Catalyzed Biaryl Coupling Mechanism

Ni-catalyzed cross-electrophile coupling (XEC) reactions have gained prominence for the construction of C–C bonds. Prior studies of XEC routes to biaryls have invoked several different mechanisms for the formation of key Ni(Ar)₂ intermediates. Here, we provide evidence for a previously unrecognized pathway involving reductively induced transmetalation between Ni^I(Ar) and Ni^II(Ar)X species. Chemical and electrochemical reduction of (^tBubpy)Ni^II(2-tolyl)Br (^tBubpy = 4,4′-di-tert-butyl-2,2′-bipyridine) to (^tBubpy)Ni^I(2-tolyl) is shown to initiate rapid transmetalation of the 2-tolyl ligand to a second equivalent of (^tBubpy)Ni^II(2-tolyl)Br, affording (^tBubpy)Ni^II(2-tolyl)₂ and (^tBubpy)Ni^IBr as well-defined products. Experimental and computational data show that the Ni^I-to-Ni^II transmetalation mechanism is much more favorable than Ni^II-to-Ni^II transmetalation. Oxidation of (^tBubpy)Ni^II(2-tolyl)Br results in rapid reductive elimination of 2-tolyl-Br, rather than promoting the analogous oxidatively induced Ni^II/Ni^III transmetalation. The Ni^II(2-tolyl)₂ product of Ni^I-to-Ni^II transmetalation is stable at room temperature, while sterically less encumbered Ni^II(Ar)₂ species undergo rapid reductive elimination to afford biaryl and a Ni⁰ byproduct. The latter species can serve as a source of electrons to promote further transmetalation and biaryl formation. The unhindered complex (^tBubpy)Ni^II(4-CF₃-phenyl)Br undergoes biaryl formation in the absence of added reductant; however, kinetic analysis reveals an induction period and autocatalytic time course. Addition of catalytic quantities of a cobaltocene-based reductant eliminates the induction period and accelerates biaryl formation, consistent with the Ni^I-to-Ni^II transmetalation pathway. The results of this study provide a new rationale for previously reported results in the literature and introduce an alternative pathway to consider in the development of Ni-catalyzed biaryl coupling reactions.