Synthesis of enantiomeric diethyl (1R,2R)- and (1S,2R)-1,2,3-trihydroxypropylphosphonates

Addition of diethyl phosphite to 2,3-O-cyclohexylidene-D-glyceraldehyde catalyzed by triethylamine or fluorides led to ca. 35:65 mixtures of diethyl (1R,2R)- and (1S,2R)-2,3-O-cyclohexylidene-1,2,3-trihydroxypropylphosphonates (4a) and (4b). Application of lithium diethylphosphonate only slightly improved diastereoselectivity. Through chromatographic separation of 4a and 4b the protected trihydroxypropylphosphonates became available for the first time as pure enantiomers. The IS configuration in the major diastereoisomer 4b was assigned on the basis of conformational and configurational analysis of 1,2-O-isopropylidene derivatives obtained from the title compounds. (C) 1998 Elsevier Science Ltd. All rights reserved.