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.