Enzyme-Mediated Preparation of (+)- and (-)-cis-alpha-Irone and (+)- and (-)-trans-alpha-Irone.

The preparation of (-)- and(+)-trans-alpha-irone (1a and 1b, resp.) and of (+)- and (-)-cis-alpha-irone (1c and 1d, resp.) from commercially available Irone alpha is reported. The relevant step in the synthetic sequence is the initial chromatographic separation of crystalline (+/-)-4,5-epoxy-4,5-dihydro-cis-alpha-irone ((+/-)-5) from oily (+/-)-4,5-epoxy-4,5-dihydro-trans-alpha-irone ((+/-)-4). The latter was subsequently converted, after NaBH4 reduction, into the crystalline 3,5-dinitrobenzoate ester (+/-)-8, thus allowing a complete separation of the two corresponding diastereoisomeric alcohol derivatives. Suitable enantiomerically pure precursors of the desired products 1a-d were obtained by kinetic resolution of the racemic allylic alcohols derived from (+/-)-5 and (+/-)-8, mediated by lipase PS (Amano). The last steps consisted of MnO2 oxidation and removal of the epoxy moiety with Me3SiCl/NaI in MeCN. External panel olfactory evaluation showed that (-)-cis-alpha-irone (1d) has the finest and most distinct 'orris butter' character.