The reaction of conjugated enyne with enolic ester is demonstrated. A DFT-based mechanistic study is conducted to determine the mechanism leading to 6-endo-trig and 5-exo-trig products with L1 and L2 ligands, respectively. Distortion/interaction analysis (DIA) and noncovalent interaction (NCI) analysis are carried out to understand the preference for a particular path with a specific ligand.

Abstract

Transition metal-catalyzed hydrofunctionalization of unsaturated bonds represents a 100% atom-economy transformation method in organic synthesis. The recently developed cascade strategy integrating hydroalkylation and hydroalkenoxylation for the hydrofunctionalization of 1,3-enynes facilitates the efficient synthesis of oxygen-containing heterocycles. In this detailed computational work, we employed density functional theory (DFT) to thoroughly investigate the effect of two different ligands, L1 (bis(2-dicyclohexylphosphinophenyl)ether) and L2 (triphenylphosphine), on the outcome of this reaction, as the use of distinct ligands results in the formation of different products, despite similar reaction conditions. With ligand L1, the reaction favored the 6-endo-trig oduct, while ligand L2 led to 5-exo-trig product formation. The DFT-based computations indicate that the rate-limiting step for 6-endo-trig product formation involves a hydride transfer from palladium hydride to C2 carbon of allene-containing enolizable carbonyl group, whereas, for exo product formation, hydride transfer from enol hydroxyl group to C1 carbon atom is rate-determining step. To understand the factors that determine why one ligand favors a particular mechanism while another ligand does not, we performed distortion/interaction analysis (DIA) and noncovalent interaction (NCI) analysis.