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 th e initial chromatographic separation of crystalline (+/-)-4,5-epoxy-4,5-dih ydro-cis-alpha-irone ((+/-)-5) from oily (+/-)-4,5-epoxy-4,5-dihydro-trans- alpha-irone ((+/-)-4). The latter was subsequently converted, after NaBH4 r eduction, into the crystalline 3,5-dinitrobenzoate ester (+/-)-8, thus allo wing a complete separation of the two corresponding diastereoisomeric alcoh ol derivatives. Suitable enantiomerically pure precursors of the desired pr oducts 1a-d were obtained by kinetic resolution of the racemic allylic alco hols derived from (+/-)-5 and (+/-)-8, mediated by lipase PS (Amano). The l ast steps consisted of MnO2 oxidation and removal of the epoxy moiety with Me3SiCl/NaI in MeCN. External panel olfactory evaluation showed that (-)-ci s-alpha-irone (1d) has the finest and most distinct 'orris butter' characte r.