Enantioselective Synthesis and Olfactory Evaluation of 13‐Alkyl‐Substituted α‐Ionones

Abstract

To study the influence of the steric bulk of the substituents at C(5) on the olfactory characteristics of alpha-ionone, the (S)-antipodes of compounds 8-10 were synthesized starting from (S)-alpha-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 C=C bond of ionones. Olfactory evaluation showed that, compared to the parent (S)-alpha-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)-alpha-ionone (1).

A Simple and Versatile Re‐Catalyzed Meyer–Schuster Rearrangement of Propargylic Alcohols to α,β‐Unsaturated Carbonyl Compounds

“…sure of enantioenriched (6S)-1 (95 % ee, 6:1 mixture of diastereomeric carbinols) [18] to 5 mol % catalyst in dimethoxyethane at 80 8C for 36 h (Scheme 4). This synthesis, further representing the most straightforward enantioselective approach to the important perfume ingredient (S)-a-ionone 2 a [21,22] nicely proved the configuration integrity of stereocenters under our conditions for the M.S. rearrangement.…”

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

“…The common synthetic strategy to give compounds 7 and 8 was at first optimized in the synthesis of α‐ionone and then extended to γ‐irone. Due to the volatility of ( S )‐α‐cyclogeraniol 11 (≥95 % ee )3g, 10 and its acetate, optimized photoisomerization of the double bond to the γ‐isomer 13 required implementation of a slightly modified Serra protocol 11. Thus, alcohol 11 3g, 10 was at first converted to the corresponding myristate 17 , which was subsequently irradiated at 254 nm for 24 h in a degassed 4:1 i PrOH/xylene mixture (Scheme ).…”

“…[2] Moreover,i onones have been employeda s valuableb uildingb locks for the preparation of more complex natural products. [3] Iononesa nd irones exist in nature as three differentr egioisomers (Figure 1), named a (1, 4), b (2, 5), and g (3,6), depending on the position of the double bond. (À)-g-Irone 8 occurs in different Iris species, for example in iris butter prepared from I. germanica; [4] in contrast, (+ +)-g-ionone 7 seems to have ar estricted distribution in nature.…”

“…We describe herein a straightforward approach to 7 and 8 from geranic acid 9 and ( S )‐epoxygeraniol 10 , respectively, which can easily be converted, in gram quantities, into enantioenriched building blocks 11 3g and 12 ,9d, 10 respectively. Our common strategy to obtain both target compounds was based on two key reactions: the photoisomerization of the endocyclic (α) double bond to the exocyclic (γ) position ( 11 → 13 and 12 → 14 , respectively),11 and a [(NHC)Au I ]‐promoted Meyer–Schuster rearrangement12 of a suitable propargylic derivative ( 15 → 7 and 16 → 8 , respectively; NHC=N‐heterocyclic carbene; Scheme ) to deliver the enone system.…”

Biomimetic Cyclization of Geraniol Derivatives, a Useful Tool in the Total Synthesis of Bioactive Monocyclic Terpenoids

“…Finally, hydroxyl group deprotection, followed by oxidation with the Dess-Martin periodinane reagent [22], uneventfully produced (S)-α-ionone 20 (ee ≥99% by GC analysis) in 65% overall yield from sulfone 27 [16]. The same procedure was also used by us, always with excellent yields, for the construction of the enone moiety of ionones 23-25 [18] and 35-38 [24,25], as well as of irones 79 and 80 [26] (vide infra).…”