Mechanistic Investigation of the Nickel-Catalyzed Transfer Hydrocyanation of Alkynes

Abstract

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(sp3)–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(sp3)–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(sp3)–CN bond to generate the active H–Ni–CN transfer hydrocyanation catalyst. Comparisons of experimentally and computationally derived 13C kinetic isotope effect data support a direct oxidative addition mechanism of the nickel catalyst into the C(sp3)–CN bond facilitated by the coordination of the second nitrile group to the nickel catalyst.

Nickel-Catalyzed Reductive Alkyne Hydrocyanation Enabled by Malononitrile and a Formaldehyde Additive

“…Oxidative addition of Ni into MPMN and subsequent β-hydride elimination would also lead to a viable H–Ni–CN species (Scheme , Hypothesis C). While the oxidative addition of Ni complexes into aryl and alkyl nitriles has been described, the use of electron-rich phosphine ligands and Lewis acids is often required, neither of which are employed in our catalytic system. − Our results are also in stark contrast to those recently reported by Morandi and co-workers, in which complete deuterium incorporation using a labeled malononitrile-based HCN donor supported a C–CN oxidative addition/β-hydride elimination mechanism . Additionally, α-phenyl acrylonitrile 23 was never observed, leading us to rule out this hypothesis as a viable pathway.…”

Nickel(BiPhePhos)-Catalyzed Hydrocyanation of Styrene—Highly Increased Catalytic Activity by Optimized Operational Procedures

“…More recent research focuses on transfer hydrocyanation at increased temperatures, utilizing the equilibrium established by the nickel catalyst. The remaining low boiling alkene can be evaporated from the reaction mixture (Figure 1) [11][12][13].…”