Synthesis of the enantiomeric forms of α- and γ-damascone starting from commercial racemic α-ionone

A straightforward synthesis of both enantiomers of α- and γ-damascone is described. The title compounds were prepared by a divergent pathway starting from the enantiomeric forms of (6RS,7SR,9RS)-7-hydroxy-7,8-dihydro-α-ionol and of (6RS,7SR,9RS)-7-hydroxy-7,8-dihydro-γ-ionol. These building blocks were obtained from racemic α-ionone in four and five steps, respectively. The 7-hydroxy group was introduced by regio- and diastereoselective epoxidation of the conjugated double bond followed by reductive opening of the oxirane ring. The hydroxy-ketone obtained was reduced diastereoselectively to trans-α-diol that could be converted to the trans-γ-diol by photochemical isomerization. Both diols were then resolved by lipase-mediated acetylation.

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(−)-(6S,7R,9S)-7-Hydroxy-α-dihydroionol acetateC15H26O3Ee = 99% (chiral GC analysis)[α]D20=-122.8(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S,7R,9S

(−)-(6S,9S)-7-Oxy-α-dihydroionol acetateC15H24O3Ee = 99% (chiral GC analysis)[α]D20=-378.4(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S,9S

(−)-α-DamasconeC13H20OEe = 99% (chiral GC analysis)[α]D20=-520.5(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S

(+)-(6S,7R,9S)-7-Hydroxy-γ-dihydroionol acetateC15H26O3Ee = 99% (chiral GC analysis)[α]D20=+25.8(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S,7R,9S

(+)-(6S,9S)-7-Oxy-γ-dihydroionol acetateC15H24O3Ee = 99% (chiral GC analysis)[α]D20=+287.4(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S,9S

(+)-γ-DamasconeC13H20OEe = 99%(chiral GC analysis)[α]D20=+272.3(c2,CHCl3)Source of chirality: lipase PS resolutionAbsolute configuration: 6S