Green-Solvent Selection for Acyl Buchwald-Hartwig Cross-Coupling of Amides (Transamidation)

Peng Lei, Yibo Wang, Yali Mu, Yujia Wang, Zhiqing Ma, Juntao Feng, Xili Liu, Michal Szostak

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The selection of solvents is essential as a suitable reaction milieu in chemical processes of industrial and academic impact. We present an evaluation of a range of green solvents for acyl Buchwald-Hartwig cross-coupling of amides to provide the first green-solvent selection guide for this powerful C-N to C-N′ cross-coupling interconversion engaging typically inert amide bonds, resulting in a net transamidation process of historically challenging amide bonds. Of the solvents considered, methyl tert-butyl ether (MTBE) and 2-methyltetrahydrofuran (2-MeTHF) were identified as the preferred alternative solvents for the acyl-Buchwald-Hartwig cross-coupling using well-defined and robust Pd(II)-NHC (NHC = N-heterocyclic carbene) precatalysts. MTBE and, in particular, 2-MeTHF are superior solvents in this cross-coupling manifold and recommended in terms of safety, health, biodegradability, and environmental score. The results indicate the replacement of hazardous solvents with green organic solvents in the biorelevant C-N to C-N′ cross-coupling manifold of amides to further the burgeoning chemical repertoire of amide-bond activation methods.

Original languageEnglish (US)
Pages (from-to)14937-14945
Number of pages9
JournalACS Sustainable Chemistry and Engineering
Issue number44
StatePublished - Nov 8 2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Renewable Energy, Sustainability and the Environment


  • 2-MeTHF
  • 2-methyltetrahydrofuran
  • Buchwald-Hartwig amination
  • N-C(O) activation
  • activated amides
  • green-solvent selection
  • methyl tert-butyl ether
  • twisted amides


Dive into the research topics of 'Green-Solvent Selection for Acyl Buchwald-Hartwig Cross-Coupling of Amides (Transamidation)'. Together they form a unique fingerprint.

Cite this