Chiral OS-dialkyl phosphoramidothioates: their preparation, absolute configuration, and stereochemistry of their reactions in acid and base

Abstract

With amines, the cis- and trans-isomers of 2-chloro-1,3,2-oxazaphospholidine-2-thiones, derived from (–)ephedrine, afford the corresponding 2-amino-derivatives which on sequential treatment with acidic alcohol, sodium hydroxide, and alkyl iodide are converted into OS-dialkyl phosphoramidothioates which are usually enantiomerically pure. In methanolic hydrogen chloride the phosphoramidothioates give the corresponding OS-dialkyl methylphosphorothioates with preponderant inversion of configuration whereas with isopropyl alcohol and hydrogen chloride OS-dialkyl isopropylphosphorothioates are formed with preponderant retention of configuration. With ethanolic hydrogen chloride, whether the P–N bond in the phosphoramidothioates is cleaved with inversion or retention of configuration is a function of the acid strength and of the substituents on nitrogen. Reactions which proceed with retention of configuration proceed by double displacements, initial formation of chloridates being followed by displacements with alcohol. Reactions of alkoxides with OS-dialkyl phosphoramidothioates, irrespective of the degree of substitution on nitrogen, proceed with preponderant inversion of configuration to afford OO-dialkyl phosphoramidates.