Preparation of Chiral Phosphonyl Compounds Using Optically Active N-[Ethoxyl(phenylthiomethyl)phosphiny1]-L-proline Ethyl Ester

Abstract

As an extension of our investigation for the preparation of optically active phosphorus compounds using L-proline ethyl ester as a chiral source(Scheme 1), the asymmetric synthesis of phenylthiomethylphosphonic acid derivatives was undertaken. The phosphonate [4] and its precursor [1] were found to be good synthetic intermediates for the preparation of various optically active phosphonates.
A diastereomeri c mixture of phosphonamidates [1 a, b ] was prepared by the reaction of ethyl phenylthiomethylphosphonochloridate with L-proline ethyl ester, which was separated efficiently to give pure [1 a ] and [1 b] by silica-gel column chromatography. The absolute configurations of both [1 a] and [1 b] were determined by the chemical correlation to ethyl methyl methylphosphonate [3] as shown in Scheme 2.
Acid-catalyzed methanolysis of [1 a] and [1 b] afford ed (S)s, -[4] and (R)s- [4], respectively. The enantiomeric excess of [4] was determined to be no less than 97% using NMR shift reagent Eu(hfc)₃. The optically active [4] was converted to ethyl methyl alkylphosphonates [5] and [6] in fair yields (Scheme 3). The phosphonate [4] was also transformed to optically active alkenylphosphonates [7] and [8] (Scheme 4). The phosphonamidates [1 a ] and [1 b] were converted to the corresponding optically active 1-propenylphosphonamidates, (E)- and (Z)- [9 a] and [9 b ] by the reaction sequences shown in Scheme 5.