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

Roman Szostak; Michal Szostak

doi:10.1021/acs.orglett.8b00086

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

Org Lett. 2018 Mar 2;20(5):1342-1345. doi: 10.1021/acs.orglett.8b00086. Epub 2018 Feb 16.

Authors

Roman Szostak¹, Michal Szostak²

Affiliations

¹ Department of Chemistry, Wroclaw University , F. Joliot-Curie 14, Wroclaw 50-383, Poland.
² Department of Chemistry, Rutgers University , 73 Warren Street, Newark, New Jersey 07102, United States.

PMID: 29450995
DOI: 10.1021/acs.orglett.8b00086

Abstract

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 (E_R < 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.

Publication types

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