Ni(I)- Ni(III) vs. Ni(II)-Ni(IV): mechanistic study of Ni-catalyzed alkylation of benzamides with alkyl halides

Nickel-catalyzed C-H bond activation has attracted significant attention for the construction of C-C bond frameworks. We report density functional theory investigations into the mechanism of nickel-catalyzed alkylation of benzamides with alkyl halides. Both the Ni(I)-Ni(III) and Ni(II)-Ni(IV) catalytic cycles were considered. The theoretical study indicated that the most feasible mechanism involved a Ni(II)-Ni(IV) catalytic cycle with four main steps: (i) N-H bond activation and (ii) C-H bond activation through the concerted metalation-deprotonation pathway, (iii) oxidative addition of BuBr to give a high-valent Ni(IV) complex, and (iv) C-C reductive elimination to generate the product and the active catalyst. The rate-determining step of the favored pathway is the oxidative addition, leading to the generation of a Ni(IV) intermediate. In addition, the present study casts light on the role of PPh3, which accelerates the cleavage of N-H bond. Frontier molecular orbital theory and natural population analysis were employed to explain the effect of the phosphine ligand on the structure of the Ni complex.