Non‐Racemic Halohydrins via Biocatalytic Hydrogen‐Transfer Reduction of Halo‐Ketones and One‐Pot Cascade Reaction to Enantiopure Epoxides

Abstract Biocatalytic hydrogen‐transfer reduction of α‐chloro‐ketones furnished non‐racemic chlorohydrins by employing either Rhodococcus ruber as lyophilized cell catalyst or an alcohol dehydrogenase preparation from Pseudomonas fluorescens DSM 50106 (PF‐ADH). For all substrates investigated, Rhodococcus ruber gave strictly the “Prelog” product, whereas PF‐ADH showed scattered stereopreference. One possibility for a follow‐up reaction of halohydrins is the ring closure to the corresponding epoxide. A novel “one pot‐one step strategy” was employed to obtain the enantiopure epoxide from the α‐chloro‐ketone in a cascade like fashion at pH>12 involving biocatalytic hydrogen transfer reduction and in situ chemo‐catalyzed ring closure.