N-Acyl-glutarimides: Effect of Glutarimide Ring on the Structures of Fully Perpendicular Twisted Amides and N-C Bond Cross-Coupling

Md Mahbubur Rahman, Chengwei Liu, Elwira Bisz, Błażej Dziuk, Roger Lalancette, Qi Wang, Hao Chen, Roman Szostak, Michal Szostak

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

N-Acyl-glutarimides have emerged as the most reactive precursors for N-C(O) bond cross-coupling reactions to date, wherein the reactivity is driven by ground-state destabilization of the amide bond. Herein, we report a full study on the effect of a glutarimide ring on the structures, electronic properties, and reactivity of fully perpendicular N-acyl-glutarimide amides. Most notably, this report demonstrates the generality of deploying N-acyl-glutarimides to achieve full twist of the acyclic amide bond, and results in the discovery of N-acyl-glutarimide amide with an almost perfect twist value, τ = 89.1°. X-ray structures of five new N-acyl-glutarimides are reported. Reactivity studies in the Suzuki-Miyaura cross-coupling and transamidation reactions provide insight into the reactivity of N-acyl-glutarimides in metal-catalyzed and transition-metal-free reactions. The effect of distortion, structures, and rotational barriers around the N-C(O) axis is discussed. The ability to achieve full distortion of the amide bond significantly expands the range of reagents available for N-C(O) cross-coupling reactions.

Original languageEnglish (US)
Pages (from-to)5475-5485
Number of pages11
JournalJournal of Organic Chemistry
Volume85
Issue number8
DOIs
StatePublished - Apr 17 2020

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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