Copper(ii)-catalyzed Chan–Lam cross-coupling: chemoselective N-arylation of aminophenols

Abstract

Copper(II)-catalyzed boronic acid promoted chemoselective N-arylation of unprotected aminophenols has been developed. Selective N-arylation of 3-aminophenol is achieved with a Cu(OAc)₂/AgOAc combination in MeOH at rt, whereas the chemoselective N-arylated products of 4-aminophenol can be obtained with a Cu(OAc)₂/Cs₂CO₃ system and benzoic acid as an additive. These ligand-free conditions and “open-flask” chemistry are robust and compatible with a wide range of functional groups. The mechanistic investigation for this selective N-arylation has been studied by considering Density Functional Theory (DFT) calculations.