Synthesis of four stereoisomers of protected 1,2-epiimino-3-hydroxypropylphosphonates

Enantiomerically pure protected 1,2-epiimino-3-hydroxypropylphosphonates were synthesised from hydroxy-1-{[(R)- or (S)-1-phenylethyl]aziridin-2-yl}methylphosphonates via regioselective ring opening with acetic acid followed by a stereospecific intramolecular cyclisation of 3-acetoxy-1-mesyloxy-2-(1-phenylethyl)aminopropylphosphonates and hydrogenolytic removal of the 1-phenylethyl group in the presence of Boc2O. The trans-isomers of 3-acetoxy-[N-(1-phenylethyl)-1,2-epiimino]propylphosphonates exist as a 2:1 mixture of invertomers, which were fully structurally characterised based on their 1H and 13C NMR spectroscopic data. Large differences in the 1JC-P values in N-(1-phenylethyl)aziridine-2-phosphonates were noticed depending on the spatial arrangement of the nitrogen lone pair and the phosphorus atom (syn-periplanar-ca. 215 Hz; anti-periplanar-182 Hz).