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

J Org Chem. 2017 Jun 16;82(12):6373-6378. doi: 10.1021/acs.joc.7b00971. Epub 2017 Jun 7.

Abstract

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 nN → 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't