Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy.
Keywords: Biocatalysis; Epoxides; Halohydrin Dehalogenase; Thiiranes; Thionation.
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