It
is significant to expand enzymatic catalysis in order to develop
efficient strategies for the synthesis of valued molecules. Herein,
an efficient enzymatic process involving the catalytic kinetic resolution
of bulky spiro-epoxyoxindoles has been developed via halohydrin dehalogenase-catalyzed
enantio- and regioselective azidolysis. The enzymatic reaction provides
a range of chiral spiro-epoxyoxindoles and 3-(azidomethyl)-3-hydroxyoxindoles
in good yields (up to 48% isolated yield) and optical purity (up to
>99% ee), both of which are useful compounds in
medicinal
and synthetic chemistry. In addition, the substrate scope has been
expanded to sterically hindered spiro-epoxyoxindoles by directed evolution
of the enzyme. Moreover, gram-scale reaction and further transformations
were also performed to demonstrate the synthetic utility and scalability
of the enzymatic kinetic resolution strategy.