Alkoxycarbonylation of α,β-unsaturated amides catalyzed by palladium(ii) complexes: A DFT study of the mechanism

The reaction mechanisms of the palladium-catalyzed alkoxycarbonylation of α,β-unsaturated amides are studied by means of density functional theory (DFT) at the B3LYP/def2-TZVP//B3LYP/def2-SVP level of theory including solvent and dispersion corrections. Two possible pathways, hydride and alkoxy, are examined and their corresponding intermediates and transition structures are calculated for the alpha and beta products. The active catalytic intermediate for the first pathway is the [Pd(ii)(PPh₃)₂(H)Cl] hydride complex, and the second considers the [Pd(ii)(PPh₃)₂(OMe)Cl] alkoxy complex as the active species. The calculations support the palladium-catalyzed alkoxycarbonylation of α,β-unsaturated amides by a three-step reaction mechanism based on palladium-alkoxy precursor, namely, the insertion of CO into the Pd-OMe bond, the insertion of the C = C amide bond into the Pd-C bond and the formation of the product, and the regeneration of the catalyst through a metathesis mechanism.