The preparation and properties of some chiral fluoromethylphosphonates, phosphonothioates, and phosphonamidothioates

Abstract

Enantiomerically pure dialkyl di- and mono-fluoromethylphosphonates are prepared by fluorination of the unsubstituted phosphonate anions. The corresponding fluoromethylphosphonothioates and thioic acids are prepared using (–)-ephedrine as a chiral template and the thioic acids are converted, via the chloridates, into the phosphoramidothioates. Treatment of O-ethyl S-methyl difluoromethyl-phosphonothioate with methoxide results in P–S bond cleavage with retention of configuration. In the corresponding monofluoromethylphosphonothioate and in S-methyl P-difluoromethyl-NN-dimethyl-phosphonamidothioate the reaction occurs with predominant inversion of configuration. Ethoxide-promoted endocyclic P–N bond cleavage in 2-difluoromethyl-1,3,2-oxazaphospholidine-2-thiones can occur with retention of configuration at phosphorus.