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

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 tertbutyl 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.

Automated summary

Solvent selection is crucial in chemical processes, and this study evaluated green solvents for acyl Buchwald-Hartwig cross-coupling, providing the first green-solvent selection guide for this process. Results identified MTBE and 2-MeTHF as preferred alternative solvents with superior properties.