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, cilt.18, sa.12, ss.2233-2241, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 12
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1039/c9ob02556a
  • Dergi Adı: ORGANIC & BIOMOLECULAR CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Biotechnology Research Abstracts, CAB Abstracts, Chimica, Compendex, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.2233-2241
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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.