Stereochemical Course of Baker's Yeast Mediated Reduction of the Tri- and Tetrasubstituted Double Bonds of Substituted Cinnamaldehydes

A comprehensive study of the stereochemical course of baker's yeast mediated reduction of substituted cinnamaldehydes is reported. Hydride addition to the beta position of beta-methylcinnamaldehydes preferentially afforded isomers of (3S)-3-phenylbutan-1-ol. The reduction of (E)-2,3-dimethylcinnamaldehyde (15) produced a mixture of (2S,3S)- and (2R,3S)-2-methyl-3-phenylbutan-1-ol (13 and 14), respectively, with 93% ee. Conversely (Z)-2,3-dimethylcinnamaldehyde (16) afforded a mixture of 13 and 14 with 33% ee. Accordingly, the reduction of trisubstituted beta-methylcinnamaldehydes 34 and 35 proceeded with the same stereochemical preference and with higher enantioselectivity to give (S)- 3-phenylbutan-1-ol (37). In addition, deuterium incorporation and H-2 NMR studies demonstrated that the addition of the second hydrogen atom to the alpha position proceeded with very low stereochemical control and the overall process is formally a mixture of cis/trans hydrogen addition to the double bond. Alternatively, alpha-methylcinnamaldehyde is reduced to (S)-2-methyl-3-phenylpropan-1-ol (24) with preferential addition of the hydride to the opposite P face with good stereochemical control of the trans addition of hydrogen to the double bond. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)