Benzyl (R)-2-(Acetylthio)Propanoate: A Promising Sulfur Isoster of (R)-Lactic Acid and Ester Precursors

Abstract

In this paper, an accessible chiral pool synthesis of benzyl (R)-2-(acetylthio)propanoate (acetylthiolactate), which is less odorous than the methyl or ethyl analogue, was performed through a clean SN2 displacement reaction using available AcSK with tris[2-(2-methoxyethoxy)]ethylamine (TDA-1), starting from commercially available benzyl (S)-lactate in 76%, 94% ee (2 steps). Deprotection of the acetyl group using N,N-dimethylethylenediamine afforded benzyl (R)-2-sulfanylpropanoate in 93% yield with 90% ee. These two sulfur-containing benzyl esters were sufficiently odorless to be purified by column chromatography. Direct HPLC analysis was applied to determine the enantiomeric excess without thiazolidin-4-one derivatizations. A complementary debenzylation of benzyl (R)-2-(acetylthio)propanoate was also performed using HBr/AcOH to afford (R)-2-(acetylthio)propanoic acid without critical racemization in 92% yield with 92% ee.

Keywords

• thiolactic ester
• benzyl (S)-lactate
• (R)-2-(acetylthio)propanoate
• SN2 displacement
• potassium thioacetate
• benzyl (R)-2-sulfanylpropanoate
• HPLC analysis
• odorless