Efficient pyrazole moiety-containing ligands for Cu-catalyzed O-arylation of phenols

Seven N2- and N3-ligands (L1–L7) were developed for the ligand-assisted CuI-catalyzed coupling reactions of aryl halides with phenols. The structural and electronic effects were studied for various combinations of pyridine and/or imine nitrogen binding sites in the ligands. 2-(1-Pyrazolyl)pyridine (L1) featuring two types of binding sites gave the best results, with yields of up to 90% at 100 °C at a catalyst loading of 10 mol% (CuI/L in 1:1 ratio). A non-radical mechanism, proposed for the L1-promoted coupling reaction, well explained the different effects of electronic nature of the substituent and steric hindrance on phenols and aryl halides.