Rhodium(iii)-catalyzed intramolecular annulations involving amide-directed C-H activations: Synthetic scope and mechanistic studies

Alkyne tethered benzamides undergo rhodium(iii)-catalyzed intramolecular annulations to give tricyclic isoquinoline derivatives in good yields. DFT calculations suggest that the reaction mechanism involves a migratory insertion of the alkyne into the rhodium-nitrogen bond of the rhodacycle intermediate that results from the initial C-H activation. This contrasts with the pathway proposed for intermolecular cases, which considers an insertion into the rhodium-carbon instead of the rhodium-nitrogen bond. The annulation is also effective with acrylamides; and, while anilides fail to participate in the process, naphthylamides do undergo the intramolecular annulation, albeit the chemoselectivity is different than for the intermolecular reactions.