Synthesis of Enantiomerically Enriched Protected 2-Amino-, 2,3-Diamino- and 2-Amino-3-Hydroxypropylphosphonates

Simple and efficient strategies for the syntheses of enantiomerically enriched functionalized diethyl 2-amino-, 2,3-diamino- and 2-amino-3-hydroxypropylphosphonates have been developed starting from, respectively, <i>N</i>-protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl (<i>R</i>)- and (<i>S</i>)-2-(<i>N</i>-Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected (<i>R</i>)- and (<i>S</i>)-2,3-diaminopropylphosphonates were synthesized from (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of (<i>R</i>)- and (<i>S</i>)-2-(<i>N</i>-Boc-amino)-3-azidopropylphosphonates using triphenylphosphine. On the other hand, treatment of the corresponding (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Bn-(aziridin-2-yl)methylphosphonates with glacial acetic acid led regiospecifically to the formation of (<i>R</i>)- and (S)-2-(<i>N</i>-Bn-amino)-3-acetoxypropylphosphonates.