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

Abstract

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.

Keywords

• aziridinephosphonates
• aziridine ring-opening
• aminopropylphosphonates
• aminohydroxypropylphophonates