A Study of Enantioselective Reduction of para-Substituted 2-Methyl-cinnamaldehydes by Baker\u27s Yeast

Reduction of a series of para-substituted 2-methyl-cinnamaldehy- des (1-7) at 20 °C and at pH = 2-3 afforded S-enantiomers of saturated alcohols 8-14 in 20-80% yield and 75 - > 99% enantiomeric excess (e.e.); at 30 °C, lower yields and e.e.s were obtained. Relative rates of the formation of allylic alcohols 15-21, catalyzed by alcohol dehydrogenase (ADH), correlate with the Hammett a+ values of para-substituents, revealing that a more efficient delocalization of the positive charge on carbonylic carbon slow down the reduction rates, whereas no correlation of the electronic properties of the substituents with the rate of C=C double bond reduction, catalyzed by enoate reductase, is observed. On reduction of 3 by dried yeast in 2H20, a,(5-carbon atoms in 10a bear 2H atoms, in accordance with the previously reported hydrogenation of selectively 2H-labeled cinnamic aldehyde and cinnamic alcohol. The accumulated data indicate that the mechanism of the enone C=C bond reduction that comprises nucleophilic attack of the hydride ion species on the (5-carbon in the first step, followed by enantioselective protonation on the a-carbon atom