Amber‐Woody Scent: Alcohols with Divergent Structure Present Common Olfactory Characteristics and Sharp Enantiomer Differentiation

Abstract

Dedicated to Dr. G¸nther Ohloff on the occasion of his 80th birthday Only one out of the four possible trans isomers of the important perfumery alcohol Norlimbanol ¾ (1) possesses a very strong amber-woody smell, the isomer 1A with (1'R,3S,6'S) absolute configuration. Its enantiomer 1B is almost odorless and devoid of amber-woody character, whereas the diastereoisomers 1C and 1D are considerably weaker and perceptible only by the most-sensitive persons. The same is true for a whole series of perceptual analogs of 1, including b-alkoxy alcohols. These ethers belong to two structural classes: [(2,2,6-trimethylcyclohexyl)oxy]-(see 3, 4, and 16) or {[2-(tert-butyl)cyclohexyl]oxy}alkan-2-ol derivatives (see 19 and 20; Table). A superimposition model allowing for good overlap of the respective hydroxylated side chains offers a tentative explanation for the shared perceptual characteristics of the two classes (Fig. 5). The lipophilic cyclohexane moieties present only a minimal overlap in this model, suggesting that quite larger molecules might possess the same smell. (S)-Configured b-alkoxy alcohols can conveniently be obtained on a larger scale by enantioselective reduction of the corresponding ketones (Scheme 9).

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

“…The transisomers 246 are responsible for the woody-steroidal powdery odor,w hile the cis-isomers 247 are weak floral. [222] In particular,t he (1'R,3S,6'S)-isomer 246 a is the main odor vector [223] with minor contributions from the (1'S,3S,6'R)isomer 246 b.…”

“…Thef irst enantioselective synthesis of the most potent (1'R,3S,6'S)-configured isomer 246 a was published in 2004 (Scheme 28). [223] Cyclization of (S)-citronellal (248)f ollowed by reduction, tosylation and substitution with KSPh afforded thioether 250,w hich was further oxidized to sulfone 251. Epoxide opening of (S)-2-propyloxirane (252)w ith lithiated sulfone 251 furnished after treatment with naphthalenyl lithium the (1'R,3S,6'S)-isomer 246 a in 99 % de with > 99 % ee.…”

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“…Es sind die trans-Isomere 246 die fürden holzigsteroidalen, pudrigen Geruch verantwortlich sind, während die cis-Isomere 247 nur schwach blumig riechen. [222] Das (1'R,3S,6'S)-Isomer 246 a ist der Hauptgeruchsvektor [223] mit geringen Beiträgen des (1'S,3S,6'R)-Isomers 246 b.…”

“…Die erste enantioselektive Synthese des stärksten (1'R,3S,6'S)-konfigurierten Isomers 246 a wurde 2004 verçffentlicht (Schema 28). [223] Die Cyclisierung von (S)-Citronellal (248) [223] Im Laufe der Jahre kamen viele verschiedene Timberol-Qualitäten mit einer immer grçßeren Menge der racemischen trans-Isomere 246 (47 %-48 %) auf den Markt, wie etwa Norlimbanol, [224][225][226] Nimberol und Karmawood (Tabelle 1), und in jüngerer Zeit sogar (3S)-angereicherte Qualitäten wie Schema 26. Die am weitesten fortgeschrittenen chemischen [202,205] und biochemischen [210] Santalolsynthesen zu fermentierten Sandelholzçlen.…”

“…Dextramber und Norlimbanol Dextro, [223] die bis zu 90-93 % der starken trans-(3S)-Isomere 246 a/b enthalten.…”