Regioselective Access to 1,2-Diarylhistidines through the Copper-Catalyzed N1-Arylation of 2-Arylhistidines

We report the copper(I)-catalyzed synthesis of 1,2-diarylhistidines through the N1-arylation of protected 2-aryl-histidines in the presence of 8-hydroxyquinoline as a ligand and aryl iodides as electrophilic coupling partners under microwave irradiation at 140 degrees C. This method provides regioselective access to previously inaccessible multisubstituted histidines with intact chirality in high yields. The synthesized 1,2-diarylated histidines are a hitherto unknown class of derivatives with untapped potential in modified amino acid based peptide and peptidomimetic drug discovery.