Highly selective asymmetric synthesis of 2-hydroxy fatty acid methyl esters through chiral oxazolidinone carboximides

Highly selective asymmetric synthesis of 2-hydroxy fatty acid methyl esters has been accomplished through chiral imide enolates. Five chiral oleic aci d imides were prepared by reaction of oleic acid with pivaloyl chloride fol lowed by reaction with five different lithiated chiral oxazolidinones inclu ding (R)-(+)-4-benzyl-2-, (S)-(-)-4-benzyl-2-, (4R,5S)-(+)-4-methyl-5-pheny l-2-, (4S,5R) -(-)-4-methyl-5-phenyl-2-, and (R)(+)-4-isopropyl-2-oxazolidi nones in 88-92% yields. The chiral imides were reacted with NaN(Mq(3)i)(2) at -78 degreesC to give enolates, which subsequently reacted with 2-(phenyl sulfonyl)-3-phenyloxaziridine to give hydroxylated products in 78-83% yield s. Methanolysis of the hydroxylated products with magnesium methoxide gave methyl 2-hydroxyoleate. Enantiomeric excesses tee) of the products were det ermined to be very high (98-99% eel by H-1 nuclear magnetic resonance study after esterification of the hydroxy group with (S)-(+)-O-acetylmandelic ac id. Enantioselective hydroxylation of other fatty acids including elaidic, petroselinic, vaccenic, and linoleic was evaluated under the similar condit ions using (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone as a chiral auxili ary to give 98% ee values for all cases.