Pd-Catalysed Direct 5-Arylation of 1-Methylpyrazole with Aryl Bromides

1-Methylpyrazole was found to be a suitable partner for palladium-catalysed direct arylation through C-H activation/functionalisation using aryl bromides. The reaction conditions and the nature of the catalyst were found to have a determining influence on the selectivity. The use of an excess of pyrazole (4 equiv), and only 0.5-1 mol% palladium(II) acetate as the catalyst, potassium acetate as the base and DMAc as the solvent, promotes the 5-arylation in moderate to high selectivities and yields. A wide variety of aryl and heteroaryl bromide derivatives have been successfully employed. Their electronic and steric properties also have an influence on the regioselectivities and yields of the coupling products. Both electron-poor and electron-rich aryl bromides gave satisfactory results, although, very congested products were obtained with lower regioselectivities.