Syntheses of the enantiomers of γ-cyclogeranic acid, γ-cyclocitral, and γ-damascone: Enantioselective protonation of enolates

Article abstract of DOI:10.1002/hlca.19950780303

(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 (+)-N-isopropylephedrine ((-)- or (+)-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.