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

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).