Enzyme-Mediated Preparation of (+)- and (-)-beta-Irone and (+)- and (-)-cis-gamma-Irone from Irone alpha.

The (-)- and (+)-beta -irones ((-)- and (+)-2, resp.), contaminated with ca. 7 - 9% of the (+)- and (-)-trans-alpha -isomer, respectively, were obtained from racemic alpha -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-alpha -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 beta -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-alpha -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-alpha -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 (1)-16 gave rise to a mixture in which the gamma -irol acetates 25a and 25b and 26a and 26b prevailed over the alpha- and beta -isomers (Scheme,le 5). The (+)- and (-)-cis-gamma -irones ((+)- and (-)-3, reap.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the alpha -double bond to the gamma -double bond. External panel olfactory evaluation assigned to (+)-beta -irone ((+)-2) and to (-)-cis-gamma -irone ((-)-3) the strongest character and the possibility to be used as dry-down note.