Mechanistic Investigation of the Nickel-Catalyzed Transfer Hydrocyanation of Alkynes

[Image: see text] The implementation of HCN-free transfer hydrocyanation reactions on laboratory scales has recently been achieved by using HCN donor reagents under nickel- and Lewis acid co-catalysis. More recently, malononitrile-based HCN donor reagents were shown to undergo the C(sp(3))–CN bond activation by the nickel catalyst in the absence of Lewis acids. However, there is a lack of detailed mechanistic understanding of the challenging C(sp(3))–CN bond cleavage step. In this work, in-depth kinetic and computational studies using alkynes as substrates were used to elucidate the overall reaction mechanism of this transfer hydrocyanation, with a particular focus on the activation of the C(sp(3))–CN bond to generate the active H–Ni–CN transfer hydrocyanation catalyst. Comparisons of experimentally and computationally derived (13)C kinetic isotope effect data support a direct oxidative addition mechanism of the nickel catalyst into the C(sp(3))–CN bond facilitated by the coordination of the second nitrile group to the nickel catalyst.