Dehydrohedione (DHH) 1 may be obtained in 20% overall yield by a Reformatsky reaction with enone methyl ether 3b, followed by acidic workup of the crude reaction mixture. Alternatively, epoxidation (3-chloroperbenzoic acid, CH2Cl2, 84% yield) of the tertiary allyl alcohol derivative 4 affords a 1 : 2 mixture of 8a and 8b. The latter epoxy ester 8b may also be obtained stereoselectively either from 4 ((BuO2H)-Bu-t, [Mo(CO)(6)], 1,2-dichloroethane, 70 degrees, 62% yield; or (BuO2H)-Bu-t, [VO(acac)(2)], decane, 20 degrees, 92% yield), or from 5 (AcOMe, LiN(SiMe3)(2), THF, -78 degrees, 84-87%). BF3 center dot Et2O-Catalyzed cascade rearrangement and OH elimination of 8a afford selectively DHH 1 in 88% yield. The cis disposition of the side chains of the weakly odoriferous hedione-like analogues 2b and 2c was maintained by means of either an epoxy or a cyclopropane moiety.

We describe in detail a direct, stereoselective synthesis of (-)-cubebol based on a Pt-, Au-, or Cu-catalyzed cycloisomerization in which control of the configuration of the propargylic center is essential for the facial selectivity. In addition, we show that cycloisomerization reactions of enantioenriched propargyl pivalates occur with substantial chirality transfer. We confirm a mechanism by means of cyclization followed by an [1,2]-acyl migration for the Pt- and the Au-catalyzed cycloisomerization. So far, no evidence supports that the Cu-catalyzed cycloisomerization follows the same reaction course.

Continuing our investigations into marine note odorants, we herein describe several new scaffolds. Among them, 2,3-dihydrobenzofuran-2-carbaldehyde is particularly interesting. The results demonstrate that the seven-membered ring with a ketone functional group of the Calone 1951® family can be replaced by a five-membered ring carrying an aldehyde function. In addition, this work has allowed us to discover the valuable 2-methoxy-4-methylphenyl methyl carbonate (20b), which is very close to vanillin, and 2-methoxy-2,4-dimethyl-1,3-benzodioxole (29d), which belongs to the isoeugenol/dihydroeugenol olfactive family.

Eight substituted indane-2-carboxaldehydes (= 2,3-dihydro-1H-indene-2-carboxaldehydes), related to conformationally constrained analogues of floral-type odorants, were synthesized in order to examine the effect of modifying the lipophilic part of the odorants (Schemes 1 and 2). None of the modified compounds showed better olfactive properties than the original ones (Tables I and 2), but an intermediate alcohol, 29, revealed itself as a valuable new member in the family of floral muguet (lily-of-the-valley)-type odorants.

The title compound (+/-)-1, a recently discovered, valuable, floral-type odorant, has been synthesized by a straightforward procedure (Scheme 1). To determine the properties of the enantiomers of 1, their separation by preparative HPLC and the determination of their absolute configuration by X-ray crystallography were carried out (Figure). Furthermore, the analogues 2-6 were synthesized, either from differently methylated 2-methylindan-1 -ones (Schemes 2 and 3) or, in the case of the 2,4,6-trimethylated homologue 6, by a completely different synthetic approach (Scheme 4). An evaluation of (+)-(S)-1, (-)-(R)-1, and (+)-1 showed only minor differences in terms of odor (Table).

The seven spirocyclic ethers 4-10, related to the tricyclic odorant Ambrox(R) (1) and its diastereoisomers 2 and 3, were synthesized. Their odoriferous activity/inactivity was correlated with the steric accessibility of the ether O-atom, calculated by computer-aided molecular modeling. The olfactory properties of the active compounds are discussed.

Nine 1,3,4,5-tetrahydro-2-benzoxepin derivatives have been prepared as mimics of the folded (gauche) conformation of cyclamenaldehyde (1) and related compounds, but none of them showed the typical lily-of-the valley (muguet) odour activity. However, conversion of these substances to previously unknown analogues of 1 having a Me substituent on the aromatic ring in an ortho position to the side chain led to new fragrance substances with remarkable properties. The results indicate that the extended (anti) conformation is more likely to be the 'bioactive' one at the receptor site(s).

AbstractEight bicyclic ether derivatives 11–18, related to the tricyclic odorant Ambrox® (1) and its analogues 2–6 by formal heteroring‐opening, have been prepared; their odoriferous activity/in activity is correlated with the steric accessibility of the ether O‐atom, calculated by computer‐aided molecular modeling.

AbstractThe characteristic odor of the diastereomers (Va) (norlimbanol) and (Vb) is configuration dependent, the trans‐alcohol (Va) being identified as the sensorily active component.

Diastereoselective Odor Perception of Alcohols in the Ionone SeriesThe characteristic odor of the diastereoisomers 1 and 2 of 1‐(2,2,6‐trimethylcyclohexyl)‐3‐hexanol is configuration dependent, the trans‐alcohol 1 being identified as the sensorily active component. Structure modification of model 1/2, for example substitution on C(2), C(13), and C(14) (ionon numbering) by CH3 groups, introduction of double bonds in the 3‐ or 4‐position, and isosteric substitution of C(7) by an O‐atom, leads to analogues revealing an unequivocal relation between stereochemistry and odor. The specific odor of alcohol 1 is generally released when all substituents are in an equatorial position; the resulting analogy with the molecular size and shape of odoriferous steroids suggests that the release of the particular scent can be correlated with a steroid‐resembling receptor event.

Structural modifications of testosterone and 19‐nortestosterone have led to the synthesis of over 60 androstane and estrane derivatives whose sensory evaluation has allowed molecular parameters to be established for release of a ‘steroid‐type’ scent. Odor perception with O‐containing compounds in both classes has been found to be regioselective. Osmophoric groups at C(3) were found to be the most active and specific. Functionality at C(2) is accompanied to a large extent by anosmic defects, and O‐containing substituents at C(1) and C(4) appear to affect the receptor membrane in exceptional cases.A further characteristic of the ‘steroid‐type’ scent is diastereoselectivity. The odor intensity of axial 2‐ and 3‐hydroxysteroids is far greater than that of the equatorial epimers, and epimeric hydroxy‐groups in the 1‐, 4‐, and 5‐positions lead to almost complete absence of odor. In addition, only steroids with ‘normal’ ring junctions and configuration were found to be odorants, whereas compounds with cis‐junctions between rings A and B, or C and D, were found to be practically inactive, Steroids therefore folow the ‘triaxial rule of odor sensation’.The most remarkable feature of our findings with steroid odorants is enantioselectivityThe term ‘regioselective’ is currently used for a reaction in which formation of one structural (or positional) isomer is favored over another. For convenience we use ‘regioselective’, ‘diastereoselective’ or ‘enantioselective’ for substrate‐receptor interactions in which one positional isomer, diastereoisomer or enantiomer leads to a different sensory response (in quality and/or intensity) than another. . Whereas with C 19 ‐steroids of the ‘natural’ enantiomeric series the perception threshold is extremely low (<6 ppb), the corresponding ‘unnatural’ enantiomers have been found essentially odorless by a panel of 30 persons. This appears to be the first reported instance of a total enantioselective response to an odorant.

AbstractDie Aceton‐sensibilisierte Photoreaktion des (‐)‐Enons (I) ergibt die optisch aktiven Produkte (II) und (III), wobei die Enantiomerenreinheit für das zurückgewonnene Enon (I) 42% und je 48% für jedes der Produkte beträgt.