Mechanochemical Solvent-Free Suzuki–Miyaura Cross-Coupling of Amides via Highly Chemoselective N−C Cleavage

Jin Zhang, Pei Zhang, Lei Shao, Ruihong Wang, Yangmin Ma, Michal Szostak

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Although cross-coupling reactions of amides by selective N−C cleavage are one of the most powerful and burgeoning areas in organic synthesis due to the ubiquity of amide bonds, the development of mechanochemical, solid-state methods remains a major challenge. Herein, we report the first mechanochemical strategy for highly chemoselective, solvent-free palladium-catalyzed cross-coupling of amides by N−C bond activation. The method is conducted in the absence of external heating, for short reaction time and shows excellent chemoselectivity for σ N−C bond activation. The reaction shows excellent functional group tolerance and can be applied to late-stage functionalization of complex APIs and sequential orthogonal cross-couplings exploiting double solventless solid-state methods. The results extend mechanochemical reaction environments to advance the chemical repertoire of N−C bond interconversions to solid-state environmentally friendly mechanochemical methods.

Original languageEnglish (US)
Article numbere202114146
JournalAngewandte Chemie - International Edition
Issue number7
StatePublished - Feb 7 2022

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)


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