Preparative-scale enzyme-catalyzed synthesis of (R)-alpha-fluorophenylacetic acid

A preparative-scale asymmetric synthesis of (R)-alpha-fluorophenylacetic ac id, a useful chiral derivatizing reagent, is described. Starting from ethyl alpha-bromophenylacetate, alpha-fluorophenylmalonic acid dipotassinm salt was prepared in three steps (54% yield), including nucleophilic substitutio n by the fluoride ion as the keystep. Both the purified form and crude prep aration of arylmalonate decarboxylase in E. coil worked well on this substr ate, and (R)-alpha-flurophenylacetic acid (>99% e.e.) was prepared in a qua ntitative yield.