Theoretical Insight into Palladium(II)–Counterion–Ligand Cooperative Regiodivergent Syntheses of Indolo[3,2‑c]coumarins and Benzofuro[3,2‑c]quinolinones from Diphenylethyne Derivatives

With two distinct active sites, 2-hydroxy-2′-amino-diphenylethyne derivatives can offer benzofuro­[3,2-c]­quinolinones via the O-attack/N-carbonylation cyclization or indolo­[3,2-c]­coumarins via the N-attack/O-carbonylation cyclization. This work presents a density functional theory-based computational study to understand the mechanism and origin of the palladium­(II)-catalyzed regiodivergent reactivity of diphenylethyne derivatives. It is indicated that the reaction features a palladium­(II)–counterion–ligand cooperative catalysis. The O-attack/N-carbonylation cyclization mainly benefits from the inductive effect of the rigid electron-withdrawing bidentate nitrogen ligand and the stabilization of the 3c-4e bond between the trifluoroacetate (TFA) anion and the hydroxyl group in the substrate for the precursor and transition state, while the viability of the N-attack/O-carbonylation cyclization stems intrinsically from the stronger nucleophilicity of the N atom as well as the important π–π interaction between the flexible electron-rich bidentate phosphine ligand and the substrate. Moreover, these calculations propose an unconventional reductive elimination mechanism for the transformation from Pd­(II) to Pd(0), where the intramolecular nucleophilic attack of the N/O atom on the carbonyl C atom results in the formal reductive elimination product. The calculated overall barriers of 14.8 kcal/mol for Pd­(TFA)₂ with the bidentate nitrogen ligand and 23.9 kcal/mol for Pd­(OTf)₂ with the bidentate phosphine ligand are qualitatively consistent with the mild experimental conditions.