Enantioselective protonation of prochiral enolates in the asymmetric synthesis of ( S)-naproxen

Abstract

Racemic methyl, iso-propyl, and tert-butyl ester derivatives of naproxen were treated with achiral LDA base to give the corresponding prochiral enolates 2 -Li, 3 -Li, and 4 -Li. Protonation of these enolates with novel chiral proton sources ( S)- 10 and ( S, S)- 11 , containing the α-phenylethylamino group, proceeded in a highly enantioselective manner. Saponification of enantioenriched ester derivatives 2– 4 afforded naproxen, ( S)- 1 , with no loss of enantiopurity.