Via a synthetic sequence consisting of PPA‐mediated Friedel−Crafts acylation of veratrol (8), Clemmensen reduction, demethylation with TMSI, Williamson ether synthesis employing 3‐chloro‐2‐(chloromethyl)prop‐1‐ene and in‐situ ruthenium tetroxide oxidation, numerous substituted benzo[b][1,4]dioxepinones 15−27 and 2,3‐dihydro‐1H‐5,9‐dioxacyclohepta[f]indenones 7, 13 and 14 were prepared to study their odor−structure correlation. In the course of these studies, we discovered the extremely powerful new marine odorant 7‐(3′‐methylbutyl)benzo[b][1,4]dioxepin‐3‐one (16). On the basis of the measured odor threshold data, an olfactophore model was constructed that rationalizes the observed odor intensities, and indicates an aliphatic hydrophobe at a distance of 6.3 Å from the centre of the aromatic‐ring binding site. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

To find new aliphatic musks, we synthesized the propionates (12), and of hydroxyacetic acid 1-(5Ј,5Ј-dimethylcyclohex-1Ј-enyl)ethyl ester (13) starting from 1-(3Ј,3Ј-dimethylcyclohex-1Ј-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),

Keywords: Fragrances / Olfactory properties / Patchouli / Spiro compounds / Structure-activity relationshipsIn the course of synthetic work on new vetiver odorants, a new, potent patchouli odorant was discovered. Its structure was elucidated as 1-hydroxy-1,4,7,7,9-pentamethylspiro-[4.5]decan-2-one (15/16), and both diastereoisomers were synthesized from the previously reported 4,7,7,9-tetramethyl-1-methylenespiro[4.5]decan-2-one by epoxidation with mchloroperoxybenzoic acid, reduction with lithium aluminum hydride, and subsequent oxidation with pyridinium chlorochromate or Dess-Martin periodinane. The 1,4-unlike-isomer 15 was found to be the diastereoisomer with the most powerful odor, and its excellent odor threshold of 0.067 ng/L air triggered the synthesis of the derivatives 19, 22, 23, and 26 possessing a different methyl substitution pattern or ring size. Glycol cleavage in the oxidation step was circumvented

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