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

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.

Graphical Abstract

Keywords:

• 1,2-Cyclic sulfates
• dihydrokavain
• lactonization
• triethylorthopropiolate

Additional information

Funding

The authors gratefully acknowledge Manisa Celal Bayar University for financial support through a project (FBE-2007-064). Manisa Celal Bayar University as the founder of our work to the Open Funder Registry data base.