Mechanistic insights into base-free nickel-catalyzed Suzuki–Miyaura cross-coupling of acid fluoride and the origin of chemoselectivity: a DFT study

Palladium-catalyzed Suzuki-Miyaura Coupling (SMC) is a powerful strategy to construct C-C bonds; however, it suffers from the disadvantages of using expensive palladium catalysts and additives. Based on the experimental development of the base-free nickel catalyzed Suzuki-Miyaura coupling of acid fluorides (ArC(O)F) with diboron reagent, we carried out DFT calculations to gain insight into the reaction mechanisms. The coupling reaction proceeds <i>via</i> four stages: (1) oxidative addition of the acid fluoride to the Ni(0) center to break the C-F bond, (2) transmetalation with diboron reagent, (3) carbonyl deinsertion <i>via</i> reverse carbonyl migratory insertion, and (4) reductive elimination to afford the coupling product and regenerate the active catalyst. It was found that the competitive rotation of the Ni-B bond and Ni-C(aryl) bond of the intermediate generated from the oxidative addition of the acid fluoride to Ni(0) center (stage I) determines the chemoselectivity of the catalytic cycle, and carbonyl migratory insertion is the rate-determining step of the coupling. Our study reveals that the PhOMe moiety in TS8 induces greater steric hindrance and reduced electronic stabilization compared to BPin in TS5, resulting in increased geometric distortion, higher distortion energy, and a less favorable transition state with a higher activation barrier. Furthermore, our computational results indicate that transmetalation prefers a concerted mechanism. Detailed analyses reveals that the strong fluorophilicity of boron enables efficient, base-free transmetalation. This study could be helpful for the development of cheap catalysts for Suzuki-Miyaura cross-coupling reactions.