Green Solvent Selection for Suzuki–Miyaura Coupling of Amides

Peng Lei*Yali MuYibo WangYujia WangZhiqing MaJuntao FengXili LiuMichal Szostak*

Abstract

A range of environmentally friendly solvents was evaluated in the Suzuki–Miyaura coupling of amides in an attempt to provide the first solvent selection guide for the powerful C–C coupling by amide bond cleavage. Of the 14 solvents and 10 Pd–NHC catalysts (NHC = N-heterocyclic carbene) considered, i-PrOAc was identified as the recommended, environmentally friendly solvent for the coupling. The obtained data permit an overall ranking of the recommended solvents in the Suzuki–Miyaura coupling of amides, with methyl t-butyl ether (MTBE), cyclopentyl methyl ether (CPME), diethyl carbonate (DEC), p-cymene, dimethylcarbonate (DMC), and anisole as alternative recommended solvents in terms of health, safety, and environmental ranking for the coupling. The data should facilitate the replacement of hazardous solvents with green organic solvents in the biorelevant manifold of amide bond coupling for the further implementation of amide bond activation methods.

Keywords

what are keywords、solvents、amide cleavage、amide activation、N−C(O) activation、Pd−NHCs、N-heterocyclic carbenes、Suzuki cross-coupling