Elucidation of the atroposelectivity in the synthesis of axially chiral thiohydantoin derivatives

Haslak Z. P., Cinar S. A., Sarigul S., Monard G., Dogan I., Aviyente V.

ORGANIC & BIOMOLECULAR CHEMISTRY, vol.18, no.12, pp.2233-2241, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 12
  • Publication Date: 2020
  • Doi Number: 10.1039/c9ob02556a
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.2233-2241
  • Acibadem Mehmet Ali Aydinlar University Affiliated: Yes


Recently, Sarigul and Dogan have synthesized a number of enantiomerically enriched axially chiral atropoisomeric 2-thiohydantoins by the reaction of c-amino acid ester salts and o-aryl isothiocyanates in the presence of triethyl amine (TEA) in dichloromethane. The non-axially chiral derivative 5-methyl-3-phenyl-2-thiohydantoin gave a racemic product whereas the axially chiral 5-methyl-3-o-bromophenyl-2-thiohydantoin was less prone to racemize at C-5 of the heterocyclic ring. In this study, we present a computational study (M06-2X/6-311-1-G(d,p) for C, H, O, N and S. M06-2X/6-3111 IG(3df,3pd) for Br) in order to propose plausible mechanisms for the racemization and cyclization steps for 2-thiohydantoin derivatives. The study includes rationalization based on steric as well as the electrostatic effects to elucidate the ep merization differences at C-5.