Computational Insights into Palladium-Catalyzed Site-Selective Anilide and Benzamide-Type [3+2] Annulation via Double C–H Bond Activation

The mechanism of palladium-catalyzed annulation reactions of benzamide- and anilide-type aromatic systems with maleimides is investigated using density functional theory. Double C–H bond activation is key to forming the desired annulation product. The first C–H bond activation for anilide- and amide-type ligands can occur at the ortho and benzylic C–H bonds, while the second C–H activation occurs at the meta carbon of the aromatic rings. For the anilide-type system, ortho and benzylic C–H bond activations occur via four- and five-membered palladacycles, respectively. In contrast, for the benzamide-type system, ortho and benzylic C–H bond activations occur via five- and six-membered palladacycles, respectively. The energy span model suggests that the initial C–H bond activation step at the benzylic position determines the turnover frequency for both anilide- and benzamide-type systems. Energy decomposition analysis and distortion-interaction/activation-strain analyses are employed to understand the electronic and steric factors controlling the turnover frequency-determining transition state.