Regiocontrolled synthesis of 1,2-diaryl-1H-imidazoles by palladium- and copper-mediated direct coupling of 1-aryl-1H-imidazoles with aryl halides under ligandless conditions

A large variety of 1,2-diaryl-1H-imidazoles, including a selective COX-2 inhibitor, have been regioselectively synthesised in moderate to high yields by direct coupling of 1-aryl-1H-imidazoles with aryl iodides or bromides in DMF in the presence of CsF and catalytic amounts of Pd(OAC)(2) under ligandless conditions. A possible mechanism for this new highly regioselective C-2 arylation reaction, involving the formation of an organocopper(I) derivatives followed by a transmetallation reaction with an arylpalladium(II) halide species and a reductive elimination, is proposed, New one-step procedures for the synthesis of 1,2,5-triaryl-1H-imidazoles, based on palladium- and copper-mediated arylation of 1-aryl-1H-imidazoles, have also been developed. Interestingly, some imidazole derivatives prepared in this study have been found to exhibit significant cytotoxic activity against some human tumour cell lines. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)