Mechanistic Study of Unprecedented Highly Regioselective Hydrocyanation of Terminal Alkynes: Insight into the Origins of the Regioselectivity and Ligand Effects

Density functional theory (DFT) calculations were performed to gain insight into the mechanism of the nickel-catalyzed hydrocyanation of terminal alkynes with Zn(CN)₂ and water to exclusively generate the branched nitrile with excellent Markovnikov selectivity. After precatalyst activation to give the LNi(0) active species, the transformation proceeds via the following steps: (1) oxidative addition of H₂O to the LNi(0) provides the intermediate LNi(II)H(OH); (2) ligand exchange of LNi(II)H(OH) with Zn(CN)₂ gives the intermediate LNi(II)H(CN); (3) alkyne insertion to the LNi(II)H(CN) forms the alkenyl nickel complex, followed by the reductive elimination step reaching the final product. This mechanism is kinetically and thermodynamically more favorable than that of the experimental proposed ones. On the basis of the experimental observations, more water molecules cannot further improve the reaction as it has also been rationalized. Furthermore, the origin of the high regioselectivity of the product, the variable effectiveness of the metal mediator as function of ligands, as well as the high yield of the alkyl-substituted alkynes substrates, is analyzed in detail.