Mechanistic Study of Suzuki–Miyaura Cross-Coupling Reactions of Amides Mediated by [Pd(NHC)(allyl)Cl] Precatalysts

Guangchen Li, Peng Lei, Michal Szostak*, Eric Casals-Cruañas, Albert Poater, Luigi Cavallo, Steven P. Nolan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


We report a combined experimental and computational investigation of the Suzuki–Miyaura cross-coupling of amides enabled by [Pd(NHC)(allyl)Cl] precatalysts. Most crucially, mechanistic details pertaining to the Pd0/NHC catalytic cycle were elucidated by computational methods. Mechanistic insights shed light on the role of each ligand about the metal. Sterics play a key role in the initial activation of the catalyst. As a key insight, we have shown that water participates in the activation of the Pd-NHC catalytic system. Easier activation has led to effect room temperature cross-coupling of a broad range of amides through selective N−C bond scission under the mildest conditions reported to date. The use of sterically hindered [Pd(IPr*)(cin)Cl] reported herein for the first time in the amide cross-coupling indicates that increasing flexible steric bulk of the isopropyl wingtip groups of the NHC ligand provides a modular scaffold for promoting amide cross-coupling in high yields. The precatalytic pathway involving both NHC ligands as well as the catalytic cycle beginning from the Pd0 species are discussed. The mechanistic details provide insight into the amide bond twist (distortion) that leads to N−C cross-coupling reactions and is required for the efficient N−C bond activation.

Original languageEnglish (US)
Pages (from-to)3096-3106
Number of pages11
Issue number14
StatePublished - Jul 19 2018

Bibliographical note

Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim


  • amides
  • cross-coupling reactions
  • density functional calculations
  • palladium
  • reaction mechanisms

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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