An efficient access to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes by Horner–Wadsworth–Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester followed by reduction with sodium borohydride

Abstract We describe a biomimetic approach to ( Z )-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes to α-fluorocinnamic thioesters by Horner–Wadsworth–Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S -ethyl ester, followed by reduction with sodium borohydride in mild conditions. The α-fluorothioesters were obtained in a good yield by condensing the aldehydes with the lithium anion of 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S -ethyl ester in THF at −78 °C. The ( E , Z )-α-fluorocinnamic thioester mixtures were then cleanly reduced with double bond isomerisation to the corresponding ( Z )-β-fluoroallyl alcohols by NaBH 4 at room temperature. This methodology may be applied to highly functionalized aldehydes as exemplified by the straightforward access to ( Z )-β-fluoroconiferin, a strong inhibitor of lignin polymerization from O -glucosylated vanillin.