Site-Selective C–H/C–N Activation by Cooperative Catalysis: Primary Amides as Arylating Reagents in Directed C–H Arylation

Direct C–H arylation of nonacidic C(sp2)–H bonds with primary amides as arylating reagents via highly chemoselective C–H/C–N/C–C cleavages has been accomplished for the first time. The key to the success is the cooperative combination of rhodium(I) catalysis and Lewis base catalysis, which can promote activation of inert C–N bonds in generic primary amides after selective N-tert-butoxycarbonyl activation in a highly efficient manner. Notably, this report constitutes the first biaryl synthesis enlisting common primary amides by N–C bond activation. This report also discloses for the first time the potential of generic, acyclic secondary amides as arylating reagents in directed C–H arylation. Considering the fundamental importance of biaryls and the key role of primary amides in organic synthesis, we expect that this concept by synergistic catalysis for aryl–aryl coupling will unlock broad catalytic applications.