Chemoenzymatic Synthesis of the Most Pleasant Stereoisomer of Jessemal

We describe the asymmetric
synthesis of the most pleasant enantiomer
of Jessemal fragrance. The key steps are (i) the one-pot reduction
of an α-chloro-tetrasubstituted cyclohexenone to give the chlorohydrin,
catalyzed by two stereoselective redox enzymes (an ene-reductase and
an alcohol dehydrogenase); (ii) the regioselective epoxide ring-opening
with organocuprate or organolithium nucleophiles. Density functional
theory calculations together with the Curtin–Hammett principle
allowed the rationalization of the regioselectivity.