Non-racemic halohydrins via biocatalytic hydrogen-transfer reduction of halo-ketones and one-pot cascade reaction to enantiopure epoxides

Biocatalytic hydrogen-transfer reduction of a.-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 alpha-chloro-ketone in a cascade like fashion at pH > 12 involving bio-catalytic hydrogen transfer reduction and in situ chemo-catalyzed ring closure.