A difluorosulfide as a Freon-free source of phosphonodifluoromethyl carbanionIn memory of Arnaud who passed away in his 25th year.

Abstract

The synthesis of difluoromethylphosphonates is becoming difficult due to environmental protective laws restricting the use of HCFCs and CFCs as starting chemicals. To circumvent this limitation, we report the preparation of a thioether as a new source of the lithiodifluoromethylphosphonate. This methodology avoiding the use of HCFCs involves a selective fluorination of sulfide followed by a thiaphilic addition of an organometallic reagent, which offers an alternative route to obtain phosphonodifluoromethyl carbanion. A contrasted reactivity, due to a medium effect, was also noted which allows addition of a wide range of electrophiles including nitroalkenes and DMF to thioethers.

Fluorophosphonylated Monomers for Dental Applications

“…17 The key step synthesis is the formation of the phosphonodifluoromethyl carbanion 6, which was trapped either with alkyl halides or reacted with tetrahydrofuran in the presence of BF 3 −Et 2 O. In the first approach, to introduce the larger, functionalized alkyl chain, the ω-hydroxy-difluoromethyl phosphonate 7 obtained by the ringopening reaction of THF was used as the main building block.…”

Synthesis of a Phosphoserine Mimetic Prodrug with Potent 14-3-3 Protein Inhibitory Activity

“…Addition of the magnesium (Waschbüsch et al, 1997) or cadmium (Qiu and Burton, 1996) reagent prepared from diethyl bromodifluoromethyl phosphonate was investigated without success. The anion prepared by reaction of diisopropyl methylthiodifluoromethylenephosphonate and t -butyllithium (Henry-dit-Quesnel et al, 2003) reacted with 1 to give the desired product 2a in 55% yield (Figure 1). However, because of the difficult preparation of the methylthio reagent and subsequent problems with selective cleavage of the isopropyl ester, we turned our attention to the generation and reaction of the lithium anion via direct deprotonation of the difluoromethylenephosphonate.…”

Synthesis of novel α-CF3-trifluoroalanine derivatives containing N-(diethoxyphosphoryl)difluoroacetyl group

“…It should be however pointed out, that no traces of products of the competing nucleophilic substitution on the phosphonate group were detectable in the crude reaction mixture as it was usually observed in some reactions of organolithium compounds with difluoromethylenephosphonate-containing molecules (Scheme 4) [13].…”