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.