Phosphine-free, palladium-catalyzed arylation of heterocycles through C-H bond activation with pivalic acid as a cocatalyst

Article abstract of DOI:10.1002/chem.200802001

A new palladium-catalyzed methodology was developed for the direct C-arylation of azoles with a broad spectrum of aryl bromides without the presence of phosphines, the aid of CuI, or other metal additives by using pivalic acid as a cocatalyst. The method also allowed the direct C-arylation of the N-heterocycle N-oxides, and to a lesser degree, the perfluoroaromatics. It was also found that the method can not only be applied to the synthesis of 8-aryl-substituted caffeines, but also 8-arylated theophyllines and theobromines. The result showed thatthe method can tolerate an array of functional groups including ester, nitrile, nitro, aldehyde, methoxy, trifluoromethyl, fluoro, and chloro substituents, and can found its applications in a number of fields such as synthetic and medicinal chemistry both in industry and in academia.