Atroposelective Synthesis of Axially Chiral Thiohydantoin Derivatives

Sarigul S. , Dogan I.

JOURNAL OF ORGANIC CHEMISTRY, cilt.81, sa.14, ss.5895-5902, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 81 Konu: 14
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1021/acs.joc.6b00696
  • Sayfa Sayıları: ss.5895-5902


Nonracemic axially chiral thiohydantoins were synthesized atroposelectively by the reaction of o-aryl isothiocyanates with amino acid ester salts in the presence of triethylamine (TEA). The synthesis of the nonaxially chiral derivatives, however, gave thiohydantoins racemized at C-5 of the heterocyclic ring. The micropreparatively resolved enantiomers of the nonaxially chiral derivatives from the racemic products were found to be optically stable under neutral conditions. On formation of the 5-methy1-3-arylthiohydantoin ring, bulky o-aryl substituents at N3 were found to suppress the C-5 racemization and in this way enabled the transfer of chirality from the alpha-amino acid to the products. The corresponding 5-isopropylthiohydantoins turned out to be more prone to racemization at C-5 during the ring formation. The isomer compositions of the synthesized axially chiral thiohydantoins have been determined through HPLC analyses with chiral stationary phases. In most cases a high prevalence of the P isomers over the M isomers has been obtained. The barriers to rotation determined around the N-sp(2)-C-aryl chiral axis were found to be dependent upon the size of the o-halo aryl substituents.