Halohydrin dehalogenase-catalysed synthesis of fluorinated aromatic chiral building blocks

Kinetic resolution of a series fluorinated styrene oxide derivatives was studied using halohydrin dehalogenase. A mutant HheC-W249P catalysed nucleophilic ring-opening with azide and cyanide ions excellent enantioselectivity (E-values up to >200), which gives access various enantiopure ?-substituted alcohols epoxides. It found that the enzyme tolerates substrates in concentrations over 50 mM. However, different side reactions were observed at elevated prolonged reaction time. The biocatalytic azidolysis cyanolysis racemic 4-trifluoromethylstyrene performed on preparative scale, affording (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol 38% yield 97% ee, (S)-3-hydroxy-3-(4-trifluoromethyl-phenyl)-propionitrile 30% 98% ee.