Synthesis and Odor of Aliphatic Musks: Discovery of a New Class of Odorants

Article abstract of DOI:10.1002/ejoc.200300578

To find new aliphatic musks, we synthesized the propionates of 2-[1′-(3″,3″-dimethylcyclohex-1″-enyl)ethoxy] -2-methylpropanol (8), of 2-[1′-(5″,5″-dimethylcyclohex -1′-enyl)-ethoxy]-2-methylpropanol (11), of hydroxyacetic acid 1-(3′,3′-dimethylcyclohex-1′-enyl)ethyl ester (12), and of hydroxyacetic acid 1-(5′,5′-dimethylcyclohex-1′-enyl)ethyl ester (13) starting from 1-(3′,3′-dimethylcyclohex-1′ -enyl)-ethanone (5) and 1-ethynyl-3,3-dimethylcyclohexanol (9). We found that the 3,3-dimethylcyclohexenyl derivatives 8 (odor threshold 0.2 ng/air) and 12 (odor threshold 0.6 ng/air) are superior musk odorants, and, thus, we constructed 1,2,4-trimethylpent-2-enyloxy analogues as seco versions. The synthesis of the esters 17-26 commenced with a Wittig-Horner-Emmons reaction of isobutyric aldehyde (14), followed by saponification, alkylation with methyllithium, LAH reduction, etherification with isobutylene oxide, and Steglich esterification. (2″E)-2′-Methyl-2′-(1″,2″ ,4″-trimethylpent-2″-enyloxy)propyl cyclopropanecarboxylate [(2″E)-19], which has a powerful and sweet musk odor and slightly fruity nuances, was found to be a typical representative of this new class of musk odorants, was subjected to co conformational analysis. In addition, we report the synthesis and olfactory properties of the related ketones 28-30, the 2-methyl-2-(1′,4′,4′-trimethylpent-2′-enyloxy)propyl esters 31-33, and the 2-(1′,4′-dimethylpent-2′-enyloxy)-2- methylpropyl esters 35 and 36. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.