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 α ‐ionone, the ( S )‐antipodes of compounds 8 – 10 were synthesized starting from ( S )‐ α ‐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 S N 2′‐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 CC bond of ionones. Olfactory evaluation showed that, compared to the parent ( S )‐ α ‐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 )‐ α ‐ionone ( 1 ).