Asymmetric Chemoenzymatic Synthesis of 1,3-Diols and 2,4-Disubstituted Aryloxetanes by Using Whole Cell Biocatalysts

Regio- and stereoselective reduction of substituted 1,3-aryldiketones, investigated in the presence of different whole cell microorganisms, was found to afford β-hydroxyketones or 1,3-diols in very good yields (up to 95%) and enantiomeric excesses (up to 96%). The enantiomerically enriched aldols, obtained with opposite stereo-preference by baker’s yeast and Lactobacillus reuteri DSM 20016 bioreduction, could then be diastereoselectively transformed into optically active syn- or anti-1,3-diols by a careful choice of the chemical reducing agent (diastereomeric ratio up to 98:2). The latter, in turn, were stereospecifically cyclized into the corresponding oxetanes in 43–98% yields and in up to 94% ee, thereby giving a diverse selection of stereodefined 2,4-disubstituted aryloxetanes.