Novel Syntheses of rac- and Enantiomerically Enriched Dimethyl α-Methylphosphoserinate

Abstract The novel synthesis of racemic and enantiomerically enriched dimethyl (S)- and (R)-α-methylphosphoserinate is described. The racemic synthesis involves a three-component reaction of hydroxyacetone, benzylamine, dimethyl phosphite and catalytic amounts of phenylphosphonic acid, or alternatively, the reaction of ethyl pyruvate with NH4OAc and dimethyl phosphite in the presence of SiO2 under solvent-free conditions, followed by reduction of the ethyl ester with NaBH4 in THF/MeOH. On the other hand, the stereoselective synthesis includes the phosphonylation of chiral cyclic imines obtained by reaction of ethyl pyruvate with (S)- or (R)-phenylglycinol, followed by reduction of the cyclic ester with NaBH4 and cleavage of the phenylglycinol fragment under hydrogenolysis. The absolute configuration is established by 2D NOESY experiments. All synthesized compounds are fully characterized.