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

Abstract

AbstractA 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 (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 (13and14), respectively, with 93 %ee. Conversely (Z)‐2,3‐dimethylcinnamaldehyde (16) afforded a mixture of13and14with 33 %ee. Accordingly, the reduction of trisubstituted β‐methylcinnamaldehydes34and35proceeded with the same stereochemical preference and with higher enantioselectivity to give (S)‐3‐phenylbutan‐1‐ol (37). In addition, deuterium incorporation and2H 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 ofcis/transhydrogen 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 thetransaddition of hydrogen to the double bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)