Enantioselective Routes to (-)-(R)-Muscone

The macrocyclic ring of muscone was prepared by Pdcatalyzed cyclization of hexadcca-l, 15-diyne, which was converted to cyclopentadec-2-enone. The stereogenic center was introduced by enantioselective Cu-catalyzed conjugate addition of dimethylzinc. Because the cc in this step was only moderate, a new route via cyclopentadeca-2, 14-dienone was developed. Enantioselective conjugate addition to this substrate led to 14-methylcylodec-2-enone, which was hydrogenated to give (-)-(R)-muscone in high overall yield with up to 98% ee.