Syntheses of the Enantiomers of γ‐Cyclogeranic Acid, γ‐Cyclocitral, and γ‐Damascone: Enantioselective protonation of enolates

Abstract

Abstract ( R )‐and ( S )‐γ‐cyclogeranic acid (( R )‐and ( S )‐ 9 , resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ‐acids ( R )‐and ( S )‐ 9 were converted into ( R )‐and ( S )‐methyl γ‐cyclogeranate (( R )‐and ( S )‐ 6 , resp.), and ( R )‐and ( S )‐γ‐damascone (( R )‐and ( S )‐ 5 , resp.). A more direct entry to ( R )‐and ( S )‐ 9 consisted in the enantioselective protonation of a thiol ester enolate with (−)‐ or (γ)‐ N ‐isopropylephedrine((−)‐ or (γ)‐ 20 ) and subsequent hydrolysis of the ( R )‐and ( S )‐ S ‐phenyl γ‐thiocyclogeranate (( R )‐ and ( S )‐ 24 , resp.; 97% ee). The esters ( R )‐ and ( S )‐ 24 were also used as precursors of ( R )‐ and ( S )‐γ‐damascone (( R )‐ and ( S )‐ 5 , resp.). Alternatively, ( S )‐ 5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (−)‐ N ‐isopropylephedrine ((−)‐ 20 ). Organoleptic evaluation demonstrated that the ( S )‐enantiomers of methyl γ‐cyclogeranate and γ‐damascone are markedly superior to their ( R )‐enantiomers.