Design and Enantioselective Synthesis of Cashmeran Odorants by Using “Enol Catalysis”

Abstract

Novel Cashmeran odorants were designed by molecular modeling. Their short syntheses involve a novel asymmetric Brønsted acid catalyzed Michael addition of unactivated α-substituted ketones. This key transformation was realized by utilizing a new type of enol activation catalysis and affords different cyclic ketones bearing α-quaternary stereocenters in good to excellent yields and with high enantioselectivity. Subsequent McMurry coupling and Saegusa-Ito oxidation furnished the enantiopure target odorants, one enantiomer of which indeed possesses the typical olfactory aspects of Cashmeran.