Enantioselective synthesis and olfactory evaluation of 13-alkyl-substituted α-ionones

To study the influence of the steric bulk of the substituents at C(5) on the olfactory characteristics of a-ionone, the (S)-antipodes of compounds 8–10 were synthesized starting from (S)-a-cyclogeraniol (14a). The latter was available in useful preparative yield with 95% ee by enantioselective lipase-PS- mediated acetylation of the racemic mixture. Key step in the conversion of 14a to 8 – 10 was an SN2’-type reaction of an organocuprate on the allylic phosphate 20, which appears to be a general method for the introduction of an alkyl substituent at the cyclohexene C1⁄4C bond of ionones. Olfactory evaluation showed that, compared to the parent (S)-a-ionone (1), the odor strength and fragrance facets of the three analogues 8–10 are significantly influenced by the bulkiness of the substituent at C(13), giving further evidence that hydrophobic interactions of this group play a significant role in the chemoreception of ionones. In particular, the odor of the ethyl derivative 8 was found to be significantly stronger than that of the parent (S)-a-ionone (1).