Abstract
Density functional theory (DFT) was employed to systematically elucidate the mechanism of the palladium-catalyzed [2 + 2 + 1] spiroannulation between 1,2-dihaloarenes, alkynes, and 2-naphthol. It is found the reaction undergoes a series of key steps, including C-I oxidative addition, alkyne insertion, C-(sp(2))-H activation, C-C coupling, C-Br oxidative addition, O-H activation, and reductive elimination, ultimately culminating in the formation of the spirocyclic product P (Pa/Pb1/Pb2). The final reductive elimination and spiroannulation process is confirmed to be the rate-determining step (RDS) under default conditions (K(3)PO(4) as the base additive and dppp as the ligand), with a free energy barrier of 33.1 kcal·mol(-1) at 130 °C. Predicted kinetics such as the half-life of reaction (20 h) are in good agreement with experimental observation of achieving 90% of spiroindanone product Pa after reacting 16 h at 130 °C. Theoretical predictions regarding the base additive effects (K(3)PO(4) and Na(3)PO(4) vs Cs(2)CO(3)) and ligand effects (dppp vs PPh(3)), as well as regioselectivity (Pb1 vs Pb2), all correspond well with experimental trends, which indicate the choice of base additive can notably influence the reaction pathway and thereby modulate the reaction efficiency and yields. These findings provide valuable insights for the optimization of reaction conditions and novel design of such transition metal-catalyzed transformations.