Theoretical Insights into the Mechanism and Ligand-Controlled Chemoselectivity of Multicomponent Carbonylation toward γ-Butenolide and Ynone

Abstract

Palladium-catalyzed multicomponent carbonylation reactions provide an efficient platform for the ligand-controlled, switchable synthesis of structurally diverse carbonyl compounds. However, the intrinsic complexity of these multicomponent catalytic systems, particularly the origin of ligand-dependent chemoselectivity, renders detailed mechanistic elucidation difficult by experiment alone. Herein, density functional theory (DFT) calculations were performed to map the full reaction mechanism and reveal the factors governing ligand-controlled chemoselectivity. Mechanistic analyses show that chemoselectivity is determined by a cooperative ligand/CuI effect at the branching point between alkyne insertion and alkyne deprotonation, thereby governing the divergent formation of γ-butenolide and ynone products. While ligand L1 favors alkyne insertion through stabilizing noncovalent interactions, ligand L2 disfavors insertion because its more rigid and sterically congested coordination environment imposes a larger steric penalty. In the L2-supported system, CuI further reinforces the preference for alkyne deprotonation by providing a less sterically congested and better aligned transition-state environment with enhanced electrostatic and orbital stabilization, ultimately leading to highly selective ynone formation. These findings provide a clear mechanistic basis for ligand/additive-controlled chemoselectivity and offer useful guidance for the rational design of switchable multicomponent carbonylation reactions.