Stereochemical course of the 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 (2)H 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.