Structures of Highly Twisted Amides Relevant to Amide N−C Cross-Coupling: Evidence for Ground-State Amide Destabilization

Vittorio Pace, Wolfgang Holzer, Guangrong Meng, Shicheng Shi, Roger Lalancette, Roman Szostak, Michal Szostak

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N−C activation/cross-coupling reactions are highly twisted around the N−C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The15N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N−C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.

Original languageEnglish (US)
Pages (from-to)14494-14498
Number of pages5
JournalChemistry - A European Journal
Volume22
Issue number41
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

Keywords

  • N−C activation
  • amides
  • rotation
  • steric hindrance
  • twisted amides

Fingerprint Dive into the research topics of 'Structures of Highly Twisted Amides Relevant to Amide N−C Cross-Coupling: Evidence for Ground-State Amide Destabilization'. Together they form a unique fingerprint.

Cite this