Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides via Site-Selective N-C Bond Cleavage by Cooperative Catalysis

Palladium-catalyzed Suzuki-Miyaura cross-coupling of primary benzamides enabled by a merger of site selective N,N-di-Boc-activation and cooperative catalysis via N-C bond cleavage for the synthesis of biaryl ketones is reported. We present the synergistic combination of Lewis base and palladium catalysis as a concept to activate inert amide N-C bonds. The mild reaction conditions provide a direct route to structurally diverse ketones. The reaction tolerates a wide range of electrophilic functional groups. Considering the fundamental importance of primary amides as pharmaceutical and synthetic intermediates, the strategy has a potential for developing a diverse array of valuable amide N-C bond functionalization reactions by the synergistic merger of Lewis base and organometallic catalysis.