Mechanism of Nickel-Catalyzed Suzuki-Miyaura Coupling of Amides

The Ni-catalyzed Suzuki–Miyaura coupling of N-tert-butoxycarbonyl (N-Boc)-protected amides provides a versatile strategy for the construction of C−C bonds. In this study, density functional theory (DFT) methods have been used to elucidate the mechanism of this reaction, with particular emphasis on the roles of N-Boc, K3PO4 and H2O. Our results corroborated those of previous reports, indicating that the overall catalytic cycle consists of three steps, including oxidative addition, transmetalation, and reductive elimination. Three of the possible transmetalation mechanisms were examined to interpret the effects of K3PO4 and H2O. According to the most feasible of these transmetalation mechanisms, K3PO4 (acting as a Lewis base) would initially interact with the Lewis acid PhBpin to give a K3PO4-PhBpin complex, which would readily undergo a hydrogen transfer step with H2O. The H transfer in the transmetalation step was determined to be the rate-determining step. Notably, the theoretical results showed good agreement with the experimental data.