Pd‐Catalyzed Hydroalkoxycarbonylation and Hydroxycarbonylation: DFT Mapping of Catalyst‐Substrate Landscape for Product Selectivity

ABSTRACT Hydroalkoxycarbonylation of internal alkenes offers a promising strategy for constructing bridged bicyclic lactones. In this work, density functional theory (DFT) calculations were employed to elucidate the detailed reaction mechanisms leading to both bridged bicyclic lactones and unsaturated carboxylic acids in Pd‐catalyzed transformations of cyclopent‐3‐en‐1‐ol derivatives. The study examines how variations in catalyst and substrate structure influence product selectivity. DFT calculations reveal that, for the formation of unsaturated carboxylic acids, the presence of a β‐hydrogen is crucial. In contrast, the pathway to bicyclic lactones diverges depending on the palladium (Pd) source. With Pd(TFA) 2 , the reaction proceeds through hydroxyl proton abstraction by TFA, followed by CO coordination, migratory insertion, and intramolecular cyclization. With PdBr 2 , the mechanism involves dissociation of bromide, associative addition of the OH group, CO binding, migratory insertion, conformational rotation, intramolecular cyclization, and reductive elimination. Furthermore, the IGM and ring strain energy analysis provides valuable insights into the interplay between catalyst design and substrate structure in dictating selectivity, thereby advancing the understanding of mechanistic factors that govern product distribution in these transformations.