Synthesis of (α,α-Difluoropropargyl)phosphonates via Aldehyde-to-Alkyne Homologation

An
efficient synthetic methodology to a series of novel alkynes
bearing a difluoromethylenephosphonate function via a Corey–Fuchs-type
sequence starting from (diethoxyphosphoryl)­difluoroacetic aldehyde
is described. Dehydrobromination of the intermediate (3,3-dibromodifluoroallyl)­phosphonate
with potassium tert-butoxide gave rise to the corresponding
bromoalkyne, whereas upon treatment with lithium base, the generation
of ((diethoxyphosphoryl)­difluoropropynyl)lithium has been achieved
for the first time. The synthetic potential of this lithium reagent
was further demonstrated by its reactions with selected electrophiles
such as aldehydes, ketones, triflates, chlorophosphines, and chlorosilanes,
leading to the corresponding propargyl phosphonates in good to excellent
yields. However, in the case, of sterically hindered aldehydes, (α-fluoroallenyl)­phosphonates
were the solely isolated products.