An Electroenzymatic Platform toward Enantioenriched α-Chloro- and α,α-Dichloro β-Hydroxy Esters

Enantioenriched α-halo- and α,α-dihalo β-hydroxy esters serve as versatile building blocks for various bioactive molecules and pharmaceutical ingredients. We developed an electroenzymatic sequential platform for the synthesis of enantioenriched α-chloro- and α,α-dichloro β-hydroxy esters using the readily available β-keto esters. The protocol integrates electrochemical selective chlorination with enzymatic reduction catalyzed by an engineered ketoreductase AxSDR M3, delivering target products in isolated yields up to 74% with excellent enantioselectivities (up to >99% ee).