Synthesis of activated alkenes bearing the difluoromethylenephosphonate group: a range of building blocks for the synthesis of secondary difluorophosphonates

Active methylene compounds reacted readily with stable hydrate 2-diethoxyphosphoryl-2,2-difluoroethane-1,1-diol to afford a range of activated alkenes bearing the difluoromethylenephosphonate group, a useful motif in the synthesis of phosphate ester mimics of biological interest. Wadsworth-Horner-Emmons reactions were employed using modified Rathke conditions for the syntheses of alkenoates, an alkenoic acid and a vinyl sulfone, while a Henry reaction followed by E1(c)B dehydration afforded an enedioate and a nitroalkene. A vinyl sulfoxide was less straightforward to synthesise and dephosphorylation to a difluoromethyl congener accompanied attempts to force the reaction to completion.