A Novel Intramolecular Horner-Wadsworth-Emmons Reaction: A Simple and General Route to α-Fluoro-α,β-unsaturated Diesters

Article abstract of DOI:10.1021/jo00102a038

Diethyl (fluorocarbethoxymethyl)phosphonate (1), prepared from triethyl phosphite and ethyl bromofluoroacetete, reacts with n-butyllithium in THF to give the phosphonate carbanion 2.Addition of the pregenerated carbanion 2 to a THF solution of methyl or ethyl oxalyl chloride at -78 deg C forms the acylated phosphonate (EtO)2P(O)CF(COCO2R)CO2Et (3).In situ reaction of 3 with Grignard reagents affords α-fluoro-α,β-unsaturated diesters R'(CO2R)C=CFCO2Et in moderate to good yields with high E-stereoselectivity.The reaction is applicable to primary, secondary, and tertiary alkyl, alkenyl, alkynyl, aryl, cyclohexyl, and perfluorinated Grignard reagents.The assignment of E and Z configuration is based on NOE experiment.The E/Z ratio of unsaturated diesters formed in the reaction varies with the metal ion and cosolvent.However, solvents and bases have little influence on the stereoselectivity.