Palladium-Catalyzed Ligand-Free C-N Coupling Reactions: Selective Diheteroarylation of Amines with 2-Halobenzimidazoles

2-Aminobenzimidazoles are widely present in a number of bioactive molecules. Generally, the preparation of these molecules could be realized by the mono-substitution of 2-halobenzimidazoles with amines. However, rare examples were reported for the di-substituted products and the selectivity of mono- vs. di-substitution was relatively low. Considering the potential values of the di-substituted products, we accomplished the first selective diheteroarylation of amines with 2-halobenzimidazoles. Notably, this Pd-catalyzed transformation was realized under ligand-free conditions. Accordingly, numerous target products were efficiently produced from various aromatic or aliphatic amines and 2-halobenzimidazoles. It was worth noting that two representative products were further confirmed by X-ray crystallography. More significantly, this catalytic process could be applied to the synthesis and discovery of new bioactive compounds, which demonstrated the synthetic usefulness of this newly developed approach.