Induced Axial Chirality in Biocatalytic Asymmetric Ketone Reduction

Catalytic asymmetric reduction of prochiral ketones of type 4-alkylidene cyclohexanone with formation of the corresponding axially chiral <i>R</i>-configurated alcohols (up to 99% ee) was achieved using alcohol dehydrogenases, whereas chiral transition-metal catalysts fail. Reversal of enantioselectivity proved to be possible by directed evolution based on saturation mutagenesis (up to 98% ee (<i>S</i>)). Utilization of ketone with a vinyl bromide moiety allows respective <i>R</i>- and <i>S</i>-alcohols to be exploited as key compounds in Pd-catalyzed cascade reactions