Sterically Controlled Pd-Catalyzed Chemoselective Ketone Synthesis via N-C Cleavage in Twisted Amides

Highly chemoselective, palladium(O)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides is reported. The reaction proceeds via selective activation of the N-C(O) bond, shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. The observed reactivity is consistent with a decrease of nN -> pi*(c=o) conjugation resulting from destabilization of the amide ground state. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions.