Base-Regulated Spiroannulation: Insights into the Palladium-Catalyzed [2 + 2 + 1] Annulation of 1,2-Dihaloarenes, Alkynes, and 2‑Naphthol.

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-(sp²)-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 (K₃PO₄ as the base additive and dppp as the ligand), with a free energy barrier of 33.1 kcal·mol^-1 at

SUBMITTER: Zhong JF 

PROVIDER: S-EPMC12809289 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature