Synthetic applications of enantioselective protonation and case study for (S)-alpha-Damascone

Among the fragrance compounds synthesized by enantioselective protonation, (S)-alpha-damascone, (R)-muscone, and (SS)-Vulcanolide are the most prominent ones. (S)-alpha-Damascone has been prepared by four different procedures: from the magnesium enolate, from the lithium enolate, from the enol, and from the corresponding thiol ester. We now present a new, industrially viable protocol for the addition of allyl magnesium chloride to the 'cyclogeranoketene' by a Barbier reaction, followed by protonation of the ensuing magnesium enolate by an aggregate formed from (-)-N-isopropylephedrine, lithium isopropylate, and acetic acid, furnishing (S)-alpha-damascone in 91% yield and with 71% ee.