Enantiomerically pure phosphonate analogues of cis- and trans-4-hydroxyprolines

Abstract

All the enantiomers of O, O-diethyl 4-hydroxypyrrolidinyl-2-phosphonates, phosphonate analogues of cis- and trans-4-hydroxyprolines, have been obtained for the first time. The synthetic strategy involved 1,3-dipolar cycloaddition of ( R)- and ( S)- N-(1-phenylethyl)- C-(diethoxyphosphoryl)nitrones to allyl alcohol and separation of the corresponding O, O-diethyl 5-(hydroxymethyl)-2-(1-phenylethyl)isoxazolidinyl-3-phosphonates, which were subsequently mesylated and hydrogenated to undergo intramolecular cyclisation. Absolute configurations of the enantiomeric proline phosphonates were established after N- and O-derivatization with ( S)- O-methylmandelic acid employing the Trost model.