On the stereochemistry of the Baker's Yeast-mediated reduction of regioisomeric unsaturated aldehydes: Examples of enantioselectivity switch promoted by substrate-engineering

The Baker's Yeast (BY) reduction of (Z)-2-chloromethyl-3-arylacrylaldehydes was found to afford (R)-2-methyl-3-aryl-propanols showing high enantiomeric excess values. Deuterium incorporation experiments were performed, in order to investigate the mechanism of the bioreduction: the formation of the corresponding substituted 2-benzylacrylaldehydes, as intermediates to be effectively reduced by Baker's Yeast, was suggested. These intermediates were synthesized and submitted to BY reduction to afford the corresponding saturated (R)-alcohols, thus confirming the conclusions drawn from labelling experiments. The enantioselectivity of their bioreduction was found to be opposite with respect to that observed for the corresponding regioisomeric 2-methylcinnamaldehydes. The preparation of the two enantiomers of 2-methyl-3-aryl-propanols by fermentation of two regioisomers represents an interesting example of substrate-controlled enantioselective reaction.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The Baker's Yeast reduction of (Z)-2-chloromethyl-3-arylprop-2-enals gave enantiomerically enriched (R)-2-methyl-3-aryl-propan-1-ols. ► The mechanism of the bioreduction was investigated by labelling experiments. ► The formation of the corresponding substituted 2-benzylacrylaldehydes, as intermediates was established. ► These 2-benzylacrylaldehydes were synthesized and submitted to Baker's Yeast reduction to afford the corresponding saturated (R)-alcohols. ► The enantioselectivity of their bioreduction was opposite with respect to that of the corresponding regioisomeric 2-methylcinnamaldehydes.