Catalytic Intermolecular Functionalization of Benzimidazoles
This chapter describes contemporary strategies for selective catalytic intermolecular functionalization of the benzimidazole scaffold. Functionalization at nitrogen and position C-2 is well developed employing copper, palladium, rhodium, nickel, and cobalt catalysis. Direct CH activation is the predominant approach to C-2 functionalization. Nickel-based catalysts can activate C—O bonds in conjunction with C—H activation at benzimidazole which grants access to a very broad range of phenols and enols as convenient functionalization precursors in this chemistry. The remaining carbon positions of benzimidazoles are typically functionalized via a sequential halogenation/coupling strategy to ensure selectivity. A key success factor in enabling these chemistries has been the fine-tuning of catalyst-ligand combinations.