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

Abstract

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.

Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

“…A solvent selection guide for conducting acyl Buchwald-Hartwig transamidation reactions has recently been compiled by Lei et al In their study, an exhaustive solvent screen of alternative solvents has been conducted including 2-MeTHF, CPME, GVL, anisole, and p -cymene, see Scheme . 1,2-Dimethoxy­ethane was used as a benchmark solvent, giving 86% yield in the same transformation.…”

“…Both 2-MeTHF and MTBE showed excellent generality and applicability across a wide range of transamidation coupling partners demonstrated through a substrate screen consisting of a variety of anilines and amides bearing EDGs and EWGs. Thus, dipolar aprotics of concern in these reactions such as THF or 1,2-dimethoxy­ethane can be effectively replaced by a drop-in alternative …”

Tailor-Made POLITAG-Pd0 Catalyst for the Low-Loading Mizoroki–Heck Reaction in γ-Valerolactone as a Safe Reaction Medium

“…Moreover, it is worth noticing that our optimization study and our results have been also obtained while using a renewable and biomass derived γ-valerolactone (GVL) as a green reaction medium. In fact, replacing the commonly employed dipolar aprotic solvents with non-toxic and safe reaction media, in combination with precious metal preservation, is a key tool for translation to a more sustainable chemical production. − …”

Improving the environmental compatibility of enzymatic synthesis of sugar-based surfactants using green reaction media

“…We selected this biocatalyst regarding its specificity towards the unbranched long chain fatty acids [20] and reusability. This present work aims to investigate the feasibility of lipase-catalyzed esterification of glucose by lauric acid in 2methyltetrahydrofuran (MeTHF), an agro-solvent known for its interesting properties in terms of safety, health, biodegradability, and environmental score [21,22] and 2methyltetrahydrofuran-3-one (MeTHF-3-one) a food-grade ingredient that is used in food industries to mimic flavors [23]. Optimal conditions were studied via a PLS-surface response design.…”