Enzymatic Kinetic Resolution of Bulky Spiro-Epoxyoxindoles via Halohydrin Dehalogenase-Catalyzed Enantio- and Regioselective Azidolysis

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.