Weakly Coordinating Amide-Directed C–H Activation/Annulation with Ru(II) Catalyst for the Construction of 3-(Trifluoromethyl)isoquinolinones from Benzamides

The novel strategy utilizing ruthenium-catalyzed intermolecular cyclization of benzamides with trifluoromethylated iminosulfonium ylides to synthesize N-H-unsubstituted 3-(trifluoromethyl)isoquinolinone derivatives was developed. ¹⁵N-labeling experiments confirmed that the nitrogen atom in the product originates from the benzamide substrates, which varies from previous mechanisms, where trifluoromethyl iminosulfonium ylides serve as nitrogen donors. The present work establishes a practical route for the preparation of N-H-unsubstituted 3-(trifluoromethyl)isoquinolinone derivatives, successfully addressing the challenges of cumbersome synthetic procedures and low yields in conventional approaches.