Mechanistic Investigation of Palladium-Catalyzed Allylic C–H Activation

The mechanism for the palladium-catalyzed allylic C–H activation was investigated using a combination of experimental and theoretical methods. A Hammett study revealed a buildup of a partial negative charge in the rate-determining step, and determination of the kinetic isotope effect (KIE) indicated that the C–H bond is broken in the turnover-limiting transition state. These experimental findings were further substantiated by carrying out a detailed density functional theory (DFT)-based investigation of the entire catalytic cycle. The DFT modeling supports a mechanism in which a coordinated acetate acts as a base in an intramolecular fashion during the C–H activation step. The reoxidation of palladium was found to reach an energy level similar to that of the C–H activation. Calculations of turnover frequencies for the entire catalytic cycle for the C–H alkylation were used to acquire a better understanding of the experimental KIE value. The good correspondence between the experimental KIE and the computed KIE values allows discrimination between scenarios where the acetate is acting in an intramolecular fashion (C–H alkylation) and an intermolecular fashion (C–H acetoxylation and C–H amination).