Late-Stage Diversification of Imidazole-Based Pharmaceuticals through Pd-Catalyzed Regioselective C-H Bond Arylations.

Palladium-catalyzed C-H bond arylation of imidazoles has been applied to pharmaceuticals such as Bifonazole, Climbazole, and Prochloraz. In the presence of phosphine-free Pd(OAc)2 catalyst, aryl bromides are efficiently coupled at the C5-position of the imidazole units, which are widely decorated. Under these conditions, only C-H bond arylation reaction occurred without affecting the integrity of chemical structure of the imidazole-based pharmaceuticals. Moreover, with Bifonazole Pd-catalyzed C-H bond diarylation at the C2- and C5-positions of imidazole unit has also been performed.