Synthesis of N-Aryl Benzimidazoles by Pd-Catalyzed Amination-Heteroannulation

Significance

Reported here is a general regio­selective synthesis of N-aryl benzimidazoles by a palladium-catalyzed C-N coupling-heteroannulation from ortho-haloacetanilides and anilines. t-BuOH and K₃PO₄ were found to be the optimal combination of solvent and base, and catalysts derived from either XPhos or RuPhos with Pd₂(dba)₃ showed superior activity. The reaction displays a good functional group tolerance. The method was found to be very effective for the preparation of N-aryl benzimidazoles containing bulky groups (e.g. R² = i-Pr) at both C-2 and C-2′ positions of the N-1 aryl group. It is important to note that a direct synthesis of N-aryl benzimidazoles from haloacetanilides and anilines is achieved, whereas N-arylation on preformed imidazoles has the potential for a non-regioselective outcome.