Expanding the Scope of Alcohol Dehydrogenases towards Bulkier Substrates: Stereo-and Enantiopreference for αα Dihalogenated Ketones

Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding ,-dihalogenated ketones, obtaining optically pure ,-dichloro- or ,-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic -substituted ketones, namely -bromo- -chloro- and -chloro--fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99% ee, 63% de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45% de).