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, N -protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl ( R )- and ( S )-2-( N -Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of ( R )- and ( S )- N -Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected ( R )- and ( S )-2,3-diaminopropylphosphonates were synthesized from ( R )- and ( S )- N -Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of ( R )- and ( S )-2-( N -Boc-amino)-3-azidopropylphosphonates using triphenylphosphine. On the other hand, treatment of the corresponding ( R )- and ( S )- N -Bn-(aziridin-2-yl)methylphosphonates with glacial acetic acid led regiospecifically to the formation of ( R )- and (S)-2-( N -Bn-amino)-3-acetoxypropylphosphonates.