Site selective Heck arylation of N-vinyl-7-azaindole engineered by N-oxide activation: scope and mechanistic studies

Abstract

The palladium-catalyzed site-selective arylation of N-vinyl-7-azaindole (AI) derivatives using (hetero)iodoarenes is reported. While N-vinyl-7-azaindole displays moderate regioselectivity, predominantly favoring α-arylation, N-oxide activation (AINO) induces a complete switch to exclusive β-arylation with high E-selectivity. Control experiments and DFT studies support the mechanistic basis of this switch, which arises from the formation of distinct metallocyclic π-complexes: a five-membered complex for α-arylation and a six-membered complex for β-arylation. These findings highlight N-oxide activation as a powerful strategy to control regioselectivity in Heck-type arylations of N-vinyl-7-azaindoles. The transformation proceeds under ligand-free conditions and showcases broad substrate scope and excellent functional group tolerance.