Synthesis of nonracemic dimethyl alpha-(hydroxyfarnesyl)phosphonates via oxidation of dimethyl farnesylphosphonate with (camphorsulfonyl)oxaziridines

Several strategies for synthesis of nonracemic dimethyl alpha-(hydroxyfarne syl)phosphonate and the parent phosphonic acid have been explored. Separati on of diastereomeric derivatives prepared by esterification of racemic a-hy droxy phosphonate with (S)-(+)-O-methylmandelic acid was possible, and thes e diastereomers could be assigned absolute stereochemistry on the basis of literature precedent; However, hydrolysis to the alpha-hydroxy phosphonic a cid was accompanied by extensive isomerization. Addition of a nonracemic ph osphonamidite to farnesal also gave nonracemic material, but again hydrolys is was problematic. Oxidation of dimethyl farnesylphosphonate anion with no nracemic (camphorsulfonyl)oxaziridines was shown to be regio- and stereosel ective for formation of the a-hydroxy phosphonate. Enantiomeric excess of s imilar to 70% ee was established by conversion of the oxidation products to their (S)-(+)-O-methylmandelate derivatives. Although hydrolysis of these methyl esters was accompanied by extensive racemization, both enantiomers o f alpha-(hydroxyfarnesyl)phosphonic acid were obtained in low ee by this st rategy.