Novel Synthesis of rac- and Enantiomerically Enriched Dimethyl α-Methyl-phosphoserinate

The novel synthesis of racemic and enantiomerically enriched (S)- and dimethyl (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, dimethyl phosphite in the presence of SiO2 under solvent-free conditions, followed by the reduction of ethyl ester with NaBH4 in a THF/MeOH. On the other hand, the stereoselective synthesis involve the phosphonylation of chiral cyclic imines obtained by reaction of ethyl pyruvate with (S)- or (R)-phenylglycinol, followed by the reduction of the cyclic ester with NaBH4 and cleavage of the phenylglycinol fragment under hydrogenolysis. The absolute configuration was established by 2D NOESY experiments. All synthesized compounds were fully characterized.

Publication History

Received: 04 December 2024

Accepted after revision: 18 December 2024

Accepted Manuscript online:
18 December 2024