Effective Tools for the Metal-Catalyzed Regiodivergent Direct Arylations of (Hetero)arenes.

The direct functionalization of two different C-H bonds of the same organic molecule using different procedures - also called regiodivergent C-H bond functionalization - currently represents an important research topic in organic chemistry, as it demonstrates the versatility of C-H bond functionalization methodology. Over the last decade, the number of tools to control such regiodivergent C-H bond functionalizations has increased significantly. In this account, we will present the various tools that allowed us to arylate different positions of various (hetero)arenes, via a C-H bond functionalization, using palladium or ruthenium catalysis.

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.