Synthesis of α-(fluorophenyl)pyridine by palladium-catalyzed cross-coupling reaction

A series of alpha-(fluoro-substituted phenyl)pyridines have been synthesized by means of a palladium-catalyzed cross-coupling reaction between fluoro-substituted phenylboronic acid and 2-bromopyridine or its derivatives. The reactivities of the phenylboronic acids containing di- and tri-fluoro substituents with alpha-pyridyl bromide were investigated in different catalyst systems. Unsuccessful results were observed in the Pd/C and PPh3 catalyst system due to phenylboronic acid containing electron-withdrawing F atom(s). For the catalyst system of Pd(OAc)(2)/PPh3, the reactions gave moderate yields of 55%-80%, meanwhile, affording 10%-20% of dimerisation (self-coupling) by-products, but trace products were obtained in coupling with 2,4-difluorophenylboronic acids because of steric hinderance. Pd(PPh3)(4) was more reactive for boronic acids with sterically hindering F atom(s), and the coupling reactions gave good yields of 90% and 91% without any self-coupling by-product.