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(sp(2))-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-tertbutoxycarbonyl 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.