Enzyme-Mediated Preparation of (+)- and (−)-β-Irone and (+)- and (−)-cis-γ-Irone fromIrone alpha®

The (−)- and (+)-β-irones ((−)- and (+)-2, resp.), contaminated with ca. 7 – 9% of the (+)- and (−)-trans-α-isomer, respectively, were obtained from racemic α-irone via the 2,6-trans-epoxide (±)-4 (Scheme 2). Relevant steps in the sequence were the LiAlH4 reduction of the latter, to provide the diastereoisomeric-4,5-dihydro-5-hydroxy-trans-α-irols (±)-6 and (±)-7, resolved into the enantiomers by lipase-PS-mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)- and (−)-8 and (+)- and (−)-9, upon treatment with POCl3/pyridine, were converted to the β-irol acetate derivatives (+)- and (−)-10, and (+)- and (−)-11, respectively, eventually providing the desired ketones (+)- and (−)-2 by base hydrolysis and MnO2 oxidation. The 2,6-cis-epoxide (±)-5 provided the 4,5-dihydro-4-hydroxy-cis-α-irols (±)-13 and (±)-14 in a 3 : 1 mixture with the isomeric 5-hydroxy derivatives (±)-15 and (±)-16 on hydride treatment (Scheme 1). The POCl3/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)-13 and (±)-14, provided enantiomerically pure cis-α-irol acetate esters, from which ketones (+)- and (−)-22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)-13 and (−)-14, treated first with MnO2, then with POCl3/pyridine (Scheme 4). Conversely, the dehydration with POCl3/pyridine of the enantiomerically pure 2,6-cis-5-hydroxy derivatives obtained from (±)-15 and (±)-16 gave rise to a mixture in which the γ-irol acetates 25a and 25b and 26a and 26b prevailed over the α- and β-isomers (Scheme 5). The (+)- and (−)-cis-γ-irones ((+)- and (−)-3, resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α-double bond to the γ-double bond. External panel olfactory evaluation assigned to (+)-β-irone ((+)-2) and to (−)-cis-γ-irone ((−)-3) the strongest character and the possibility to be used as dry-down note.