Cu-catalysed Chan–Evans–Lam reaction meets deep eutectic solvents: efficient and selective C–N bond formation under aerobic conditions at room temperature

Abstract

An unprecedented, simple and general protocol for the selective formation of C–N bonds was developed by using cheap and easily available Cu(OAc)₂ as catalyst for the Cu(II)-catalysed Chan–Evans–Lam reaction in Deep Eutectic Solvents (DESs) as sustainable reaction media. The meticulous selection of both components of DES for this transformation (1ChOAc/2Urea) allows C–N coupling reactions under bench-type conditions (room temperature/under air), and in the absence of external ligands. The use of DES also permits to: (i) recycle the catalytic system for up to four consecutive runs; (ii) scale-up the C–N coupling reaction (without erosion of the yield); and (iii) apply this methodology to the synthesis of the anti-inflammatory drug Flufenamic acid (E-factor: 10).