Synthetic Applications of Enantioselective Protonation and Case Study for ( S )‐ α ‐Damascone

Among the fragrance compounds synthesized by enantioselective protonation, ( S )‐ α ‐damascone, ( R )‐muscone, and ( S , S )‐ Vulcanolide are the most prominent ones. ( S )‐ α ‐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 )‐ α ‐damascone in 91% yield and with 71% ee.