Resonance Destabilization in N-Acylanilines (Anilides): Electronically-Activated Planar Amides of Relevance in N–C(O) Cross-Coupling

Transition-metal-catalyzed activation of amide N–C(O) bonds proceeds via selective metal insertion into the carbon–nitrogen amide bond. Herein, we demonstrate that N -acylanilines (anilides), the first class of planar amides that have been shown to undergo selective amide N–C cross-coupling reactions, feature a significantly decreased barrier to rotation around the amide N–C(O) bond. Most significantly, we demonstrate that amide n N → π* C═O resonance in simple anilides can be varied by as much as 10 kcal/mol. The data have important implications for the design of N–C(O) amide cross-coupling reactions and control of the molecular conformation of anilides by resonance effects.