Mechanistic study of the cooperative palladium/Lewis acid-catalyzed transfer hydrocyanation reaction: The origin of the regioselectivity

Density functional theory (DFT) calculations have been performed to gain insights into the catalytic mechanism of the palladium/Lewis acid-catalyzed transfer hydrocyanation of terminal alkenes to reach the linear alkyl nitrile with excellent anti-Markovnikov selectivity. The study reveals that the whole catalysis can be characterizedviathree stages: (i) oxidative addition generates the π-allyl complexIM2, followed by β-hydride elimination leading to the intermediateIM4, (ii) ligand exchange followed by Pd-H migratory alkene insertion gives the anti-Markovnikov intermediateIM6and (iii)IM6undergoes a reductive elimination step to form the linear terminal nitrile3aand regenerates the active species for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible. The oxidative addition step, with a barrier of 30.9 kcal mol⁻¹, should be the rate-determining step (RDS) in the whole catalysis, which agrees with the experimental high temperature of 110 °C. Furthermore, the origin of the high regioselectivity of the product with excellent anti-Markovnikov selectivity is discussed.