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

Org Lett. 2015 Sep 4;17(17):4364-7. doi: 10.1021/acs.orglett.5b02209. Epub 2015 Aug 18.

Abstract

Highly chemoselective, palladium(0)-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 → π*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.