Synthesis of (R)- and (S)-3′-Fluorothalidomide

Significance

Interest in thalidomide has revived owing to its potential for treatment of multiple ­myeloma. The notorious teratogenicity of (S)-thalidomide cannot be avoided by using the (R)-enantio-mer, because it easily epimerizes under physio-logical conditions. 3′-Fluorothalidomide is a non-epimerizable analogue that was synthesized by enantiodivergent electrophilic fluorination using a combination of dihydroquinine B and N-fluorobenzenesulfonimide C as the key reaction.