Diastereodivergent Horner–Wadsworth–Emmons-Type Reaction of Ethyl 2-[Bis(benzylthio)phosphoryl]-2-fluoroacetate for the Synthesis of (E)- and (Z)-α-Fluoro-α,β-unsaturated Esters

Ethyl 2-[bis(benzylthio)phosphoryl]-2-fluoroacetate was synthesized as a novel Horner–Wadsworth–Emmons (HWE)-type reagent and found to afford both (E)- and (Z)-α-fluoro-α,β-unsaturated esters in a diastereodivergent manner. The HWE-type reactions of ethyl 2-[bis(benzylthio)phosphoryl]-2-fluoroacetate with aldehydes proceeded Z-selectively when NaHMDS was used in excess relative to the HWE-type reagent, yielding the corresponding (Z)-α-fluoro-α,β-unsaturated esters as the major product with E/Z ratios of up to 1:100. Conversely, when the HWE-type reagent was used in excess relative to NaHMDS, the stereoselectivity of the HWE-type reactions shifted markedly from Z to E, with E/Z ratios of up to 98:2.