Preparation of some chiral alkyl alkyl phosphorothioates and stereochemical studies of their conversion into other chiral organophosphates

Abstract

(2R,4S,5R)-2-Chloro-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine-2-thione (1) obtained as a pure isomer following crystallisation of the product from (–)-ephedrine and PSCl₃, is readily converted on sequential treatment with sodium ethoxide, methanolic HCl, and sodium hydroxide into optically pure (+)-(R)-ethyl methyl hydrogen phosphorothioate. The enantiomeric (–)-(S)-ethyl methyl hydrogen phosphorothioate is formed from (1) by reversing the order of alcohol addition. The route to alkyl alkyl hydrogen phosphorothioates is a general one since other alcohols may be used in place of methanol and ethanol. The alkyl alkyl hydrogen phosphorothioates are converted stereoselectively into alkyl alkyl phosphorothiochloridates and alkyl alkyl phosphorochloridates and the chloridates are converted stereoselectively into other products. Whether reactions occur preponderantly with retention or inversion of configuration is established and the degree of stereoselectivity of all reactions is measured by an n.m.r. method using a chiral shift reagent.