A Practical, Enantioselective Synthesis of the Fragrances Canthoxal and Silvial®, and Evaluation of Their Olfactory Activity

The fragrances ( S )-(+)- and ( R )-(–)-canthoxal [( S )-(+)- and ( R )-(–)-3-(4-methoxyphenyl)-2-methylpropanal] and (+)- and (–)-Silvial ® [(+)- and (–)-3-(4-isobutylphenyl)-2-methylpropanal] have been synthesized in high enantiopurity via a simple four-step strategy starting from the commercially available 4-substituted benzaldehydes. The key synthetic step is the catalytic asymmetric hydrogenation of the appropriate 3-aryl-2-methylacrylic acid which has been carried out employing an in situ prepared ruthenium/axially chiral phosphine catalyst (up to 98% ee). The olfactory activity of the single enantiomers has been evaluated.