Synthesis of four enantiomers of 2,3-di( N-Boc-amino)-1-hydroxypropylphosphonates

Abstract

Enantiomerically pure diethyl (1 S,2 R)-, (1 S,2 S)-, (1 R,2 R)- and (1 R,2 S)-2,3-di( tert-butoxycarbonyl)amino-1-hydroxypropylphosphonates were synthesised from diethyl (1 S,2 R,1′ S)-, (1 S,2 S,1′ R)-, (1 R,2 R,1′ S)- and (1 R,2 S,1′ R)-[ N-(1-phenylethyl)]-2,3-epimino-1-hydroxypropylphosphonates, respectively, via aziridine ring opening with neat TMSN 3 followed by hydrogenolysis in the presence of Boc 2O. A plausible mechanism for the aziridine ring opening in 2,3-epimino-1-hydroxypropylphosphonates involving the intermediate aziridinium ions was proposed. Significant differences in the rates of the aziridine ring opening between diastereoisomeric phosphonates (1 S,2 R,1′ S) and (1 S,2 S,1′ R) were rationalised taking into account different conformations of the 1-phenylethyl group in both diastereoisomers.