Electrophilicity Scale of Activated Amides: 17O NMR and 15N NMR Chemical Shifts of Acyclic Twisted Amides in N−C(O) Cross-Coupling

Laura Ielo, Vittorio Pace, Wolfgang Holzer, Md Mahbubur Rahman, Guangrong Meng, Roman Szostak, Michal Szostak

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The structure and properties of amides are of tremendous interest in organic synthesis and biochemistry. Traditional amides are planar and the carbonyl group non-electrophilic due to nN→π*C=O conjugation. In this study, we report electrophilicity scale by exploiting 17O NMR and 15N NMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selective oxidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acid anhydrides and acid chlorides. Furthermore, a wide range of electrophilic amides is possible with gradually varying carbonyl electrophilicity by steric and electronic tuning of amide bond properties. Overall, the study quantifies for the first time that steric and electronic destabilization of the amide bond in common acyclic amides renders the amide bond as electrophilic as acid anhydrides and chlorides. These findings should have major implications on the fundamental properties of amide bonds.

Original languageEnglish (US)
Pages (from-to)16246-16250
Number of pages5
JournalChemistry - A European Journal
Issue number69
StatePublished - Dec 9 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry


  • N-C(O) activation
  • O NMR spectroscopy
  • cross-coupling
  • transition-metal catalysis
  • twisted amides


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