Copper-DMEDA Catalyzed Carbon-Sulfur Bond Formation for the Derivatization of 5-(3,4,5-Trimethoxyphenyl)-1,3,4-oxadiazole-2-thiol

Abstract

Sulfide linkage plays an important role not only in synthetic chemistry but also has vast applications in drug discovery as a pharmacologically active moiety. Transition metal-catalyzed thiolation is a challenging task as sulfur has a high affinity to bind with transition metal catalysts resulting in catalyst poisoning. Catalyst poisoning results in the inhibition of the reactivity and utility of the reactions. In the current work, a simple and facile method is developed to carry out S-arylation using hetero-aryl thiols and substituted aryl iodides. The reaction conditions were optimized using varied combinations of transition metal catalysts and ligands. The different copper sources included CuCl, CuI, and Cu(OAc)2 different bidentate nitrogen-based ligands including bipyridine, di-tert-butylbipyridine, DMEDA, and sarcosine. The optimized condition consists of CuI as the catalyst and DMEDA as a ligand. The reaction was found to be optimum for a range of aryl iodides in the presence highly basic oxadiazole ring. The coupled products were isolated in excellent yields and show excellent functional group tolerance bearing -NO2, -Cl, -OCF3 groups.