Access to 2-(Trifluoromethyl)indoles via Pd(0)-Catalyzed Intramolecular Cyclization of Trifluoroacetimidoyl Chlorides with Alkynes

A novel Pd(0)-catalyzed intramolecular 5-exo-dig cyclization between trifluoroacetimidoyl halides and alkynes has been established, involving a key alkyne oxypalladation process with H₂O serving as the nucleophile. This protocol exhibits broad functional group tolerance under mild conditions, providing 2-(trifluoromethyl)indole derivatives in moderate to excellent yields. Notably, the streamlined synthesis of a trifluoromethylated pravadoline analogue and the anticancer bioactivities of three products highlight the potential of this methodology for practical applications.