The synthesis of chiral sulfahydantoins. Stereochemical aspects and regiospecific protection

Article abstract of DOI:10.1016/S0040-4020(01)80506-8

The enantiospecific synthesis of N²-benzyl-1-thia-2,5-diazolidin-3-one dioxides (sulfa-analogues of hydantoins) was carried out through two convergent pathways starting from chlorosulfonyl isocyanate (CSI) and chiral α-amino- and hydroxyesters. The intermediate carboxylsulfamides (containing 'activated sulfamoyl group') react easily in the Mitsunobu conditions to give ultimately the N-protected sulfa-hydantoins, or symmetric and dissymmetric sulfones of bis-N-aminoesters. The non-racemization during the cyclization of N-sulfamylaminoesters in alkaline conditions was established by chemical and spectroscopic methods (nmr with chiral Eu(hfc)₃.