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 β position of β‐methylcinnamaldehydes preferentially afforded isomers of (3 S )‐3‐phenylbutan‐1‐ol. The reduction of ( E )‐2,3‐dimethylcinnamaldehyde ( 15 ) produced a mixture of (2 S ,3 S )‐ and (2 R ,3 S )‐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 β‐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 α 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, α‐methylcinnamaldehyde is reduced to ( S )‐2‐methyl‐3‐phenylpropan‐1‐ol ( 24 ) with preferential addition of the hydride to the opposite β face with good stereochemical control of the trans addition of hydrogen to the double bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)