Regioselective access to 1,2-diaryl histidines via copper-catalyzed N(1)-arylation of 2-aryl histidines

We report copper(I)-catalyzed synthesis of 1,2-diaryl histidines via N(1)-arylation of protected 2-aryl histidines in the presence of 8-hydroxyquinoline as ligand and aryl iodides as electrophilic coupling partners, under microwave irradiation at 140 oC. This methodology provides regioselective access to previously inaccessible multi-substituted 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 acids-based peptides and peptidomimetics drug discovery.