N-Acyl-glutarimides: Resonance and Proton Affinities of Rotationally-Inverted Twisted Amides Relevant to N-C(O) Cross-Coupling.

Resonance energies and proton affinities of N-acyl-glutarimides, compared with related twisted acyclic amides of relevance to N-C(O) cross-coupling, are reported. The data demonstrate that amidic resonance in N-acyl-glutarimides practically disappears (ER < 2.8 kcal/mol), while, intriguingly, these amides favor O-protonation despite significant twist. In some cases, N-acyl-glutarimides undergo intramolecular N- to O-acyl migration, indicative of high capacity as acylating reagents. The understanding provided for the high reactivity of N-acyl-glutarimides should facilitate the development of a broadly general N-C(O) amide activation platform.