biostudies-literatureUnknown11(1)Zhong JFDensity 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 <b>P</b> (<b>Pa</b>/<b>Pb1</b>/<b>Pb2</b>). 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 ACS omega980-994https://www.ebi.ac.uk/biostudies/studies/S-EPMC12809289biostudies-literatureBase-Regulated Spiroannulation: Insights into the Palladium-Catalyzed [2 + 2 + 1] Annulation of 1,2-Dihaloarenes, Alkynes, and 2‑Naphthol.PMC12809289Hu ZTFeng XYDuan LFShi YBZhong JFMu WHLi JYLiu GfalseBase-Regulated Spiroannulation: Insights into the Palladium-Catalyzed [2 + 2 + 1] Annulation of 1,2-Dihaloarenes, Alkynes, and 2‑Naphthol.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 <b>P</b> (<b>Pa</b>/<b>Pb1</b>/<b>Pb2</b>). 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 2026-01-01T00:00:00Z2026 Jan2026-06-06T16:07:36.824Z2026-06-02T03:11:12.364ZS-EPMC128092894155245810.1021/acsomega.5c08037