Asymmetric synthesis of (S)-dihydrokavain from l-malic acid

ESKİCİ M., Karanfil A., ÖZER M. S., Kabak Y., Durucasu İ.

Synthetic Communications, vol.48, no.18, pp.2382-2390, 2018 (SCI-Expanded, Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 48 Issue: 18
  • Publication Date: 2018
  • Doi Number: 10.1080/00397911.2018.1489057
  • Journal Name: Synthetic Communications
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2382-2390
  • Keywords: 1,2-Cyclic sulfates, dihydrokavain, lactonization, triethylorthopropiolate
  • Manisa Celal Bayar University Affiliated: Yes

Abstract

A practical and efficient asymmetric synthesis of (S)-dihydrokavain from known ethyl (S)-2-hydroxy-4-phenylbutanoate which is, in turn, readily available from l-malic acid as a cheap chiral pool material is described using regioselective ring-opening of the 1,2-cyclic sulfate with lithium-3,3,3-triethoxypropiolate and subsequent HgO/H2SO4-mediated lactonization as the key steps. Its opposite enantiomer (R)-dihydrokavain was also synthesized from d-malic acid using the same sequences of reactions for the purpose of optical purity determination.