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

Abstract

We report the copper(I)‐catalyzed synthesis of 1,2‐diarylhistidines through the N1‐arylation of protected 2‐arylhistidines in the presence of 8‐hydroxyquinoline as a ligand and aryl iodides as electrophilic coupling partners under microwave irradiation at 140 °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.