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

Abstract

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.