Deep Eutectic Solvent And Water As Two Environmentally Benign And Recyclable Reaction Media For Efficient Goldberg–Type C–N Coupling Reactions.

In recent years, the applications of Cu-based catalyst, which are based on the earth-abundant and inexpensive copper metal, have generated a great deal of interest in several areas i) cross-coupling reaction,1 ii) asymmetric synthesis,2 iii) C-N bond formation,3 iv) Ullman-type coupling reactions.4 Building on these findings, in collaboration with the group of García-Álvarez, we have recently investigated copper-catalysed Goldberg-type reactions,5 aimed at forging C–N bonds, in unconventional, environmentally responsible solvents, like water and the so-called Deep Eutectic Solvents (DESs). In this communication, we report on the synthesis of functionalised amides by reacting aryl halides with aromatic or primary/secondary aliphatic amides, when working either in water or in choline chloride (ChCl)-based DESs. Under aerobic conditions and mild heating, this coupling proceeds with high chemoselectivity, when using CuI as the catalyst, KOH as a base, and ethylene diamine as a bidentate ligand, with the desired adducts isolated in up to 99% yield. The applicability of the methodology was further validated with (a) the scale up of the reaction, (b) the recyclability of both the catalyst and the eutectic mixture, and (c) the synthesis of biologically active molecules