Mechanistic Insight into the Ni-Catalyzed Kumada Cross-Coupling: Alkylmagnesium Halide Promotes C–F Bond Activation and Electron-Deficient Metal Center Slows Down β-H Elimination

The Ni-catalyzed Kumada-Tamao-Corriu (KTC) cross-coupling between aryl fluorides and alkyl Grignard reagents has been used to achieve a highly selective Csp2-Csp3 bond construction via the carbon-fluorine (C-F) bond activation. However, the detailed mechanism of this groundbreaking KTC reaction remains unclear. Herein, we perform a series of analyses by density functional theory (DFT) calculations in order to understand the reaction mechanisms for the selective activation of a highly inert C-F bond by Ni catalysts with bidentate phosphorus ligands. An alternative mechanism for Ni/Mg bimetallic cooperation C-F bond cleavage instead of a traditional oxidative addition was proposed. The push-pull interaction in the transition state provided by the Ni center and the Lewis acid of the Mg cation smoothly breaks the C-F bond, supported by the significantly decreased activation energy from 30.9 to 4.6 kcal mol-1 and principal interacting orbital analysis. Owing to the elevated lowest unoccupied molecular orbital energy level and the electron-deficient metal center caused by the bidentate phosphorus ligand, the β-H elimination could be impeded, increasing the selectivity of KTC cross-coupling. Our DFT results rationally explain the experimental observations, which will be helpful for further development of KTC cross-coupling.