The steric influence of fluorine compared to hydrogen in enzymatic sys
tems is probed by the resolution of a series of fluorinated benzhydrol
acetates with lipases. Lipase AY-Amano-30 from Candida cylindracea ca
n distinguish a single fluorine atom and the discrimination is most si
gnificant with fluorine in the ortho position close to the reaction ce
ntre. Increasing the number of fluorine atoms improves the discriminat
ion and 2,3,4,5,6-pentafluoroaryl benzhydrol was resolved in 86%ee aft
er 35% conversion.