The synthesis, absolute configuration, and olfactive evaluation of (-)-(E)-alpha-trans-bergamotenone (=(-)-(1'S,6'R,E)-5-(2',6'-dimethylbicyclo[3.1.1]hept-2'-en-6'-yl)pent-3-en-2-one; (-)-1), as well as its homologue (-)-19 are reported. The previously arbitrarily attributed absolute configuration of 1 and of (-)-alpha-trans-bergamotene (=(-)-(1S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1.1]hept-2-ene; (-)-2), together with those of the structurally related aldehydes (-)-3a,b and alcohols (-)-4a,b, have been rigorously assigned.

The beta-dienoate (+)-(5S)-13a (86% ee; meaning of alpha and beta as in alpha- and beta-irone, resp.) was obtained from (-)-(5S)-9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)-15/(+)-(1R,5S)-15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the alpha-isomer (-)-(R)-16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl4-catalyzed stereospecific cyclization of (+)-(Z)-6 to (+)-trans-8a (Scheme 2), followed by a diastereoselective epoxidation to (+)-11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (-)-12, the same ester (+)-13a (Scheme 3), but with poor optical purity (13 % ee), due to an initial rapid [1,2]-H shift. The absolute configuration of(-)-16a-c was confirmed by chemical correlation with (-)-trans-19 (Scheme 4). C-13-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.

Treatment of ten monocyclic dienols 8-11 with an excess of fluorosulfonic acid in 2-nitropropane at -90-degrees afforded diastereoisomeric mixtures of racemic tricyclic ethers 12-14 in 81-91 % yield (see Tables 1 and 2). These transformations represent further examples of biomimetic acid-mediated cyclisations in which an OH group serves as the internal nucleophilic terminator. A non-synchronous process is postulated, and the examples described strongly re-inforce our working mechanistic hypothesis, whereby the stereochemical course of cyclisation is directed by the orientation of the side chain vicinal to the intermediate cyclohexyl cation (see Schemes 4 and 5). It is also demonstrated that the efficiency of this process is independent of the nature of the OH group, which may be primary, secondary, or tertiary. In addition, the organoleptic properties of 12 14, Me homologs of known odorants such as Ambrox(R) ((-)-3a) and its diastereoisomers, are briefly discussed.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Flash-vacuum thermolysis of the four diastereoisomeric 5,6-epoxy-5,6-dihydro-caryophyllenes 1-4 at 500-550 degrees/0.1-0.7 Torr leads to the hitherto unreported enantiomers of (6RS,7RS)- and (6RS,7SR)-6,7-epoxy-6,7-dihydro-beta-farnesenes ((+/-)-5 and (+/-)-6, resp.). In particular, (+)-5 is formed in 45% yield (ca. 90% ee) and is, thus, an attractive chiral building block for natural-product synthesis.

Treatment of 10 structurally related trienols and dienols 5-8 with an excess of fluorosulfonic acid in 2-nitropropane at -90-degrees-C afforded, in 74-87% yield, diastereoisomeric mixtures of the odoriferous norlabdane oxides 9-15 ((-)-9 (Ambrox) is a naturally occurring ambergris odorant). These transformations represent examples of efficient biomimetic acid-mediated cyclizations in which the hydroxyl group serves as the internal nucleophilic terminator. The stereochemical outcome of these kinetically controlled processes has been analysed in detail, and mechanistic hypotheses consistent with the results have been proposed. For the four acyclic trienols 5, the major reaction pathway can be rationalized by a totally synchronous process involving three internal anti additions via chair or skew-boat conformations of the nascent cyclohexane rings. An alternative explanation postulates a non-synchronous process in which ring closure to an intermediate cyclohexyl cation is followed by rapid cyclization, directed by a strong kinetic preference for equatorial C-C and C-O ond formation. In contrast, for the monocyclic dienols 6-8 only a nonsynchronous process, involving prior protonation of the cyclohexenyl bond, is fully consistent with the results. In the nonsynchronous processes, the orientation of the side chain vicinal to the cyclohexyl cation directs the stereochemical course of the cyclization. For the acyclic trienols, this factor is predetermined by the configuration of the C(7) = C(8) bond, whereas, for the acyclic trienols, this factor is predetermined by the configuration of the C(7) = C(8) bond, whereas, for the monocyclic dienols, this orientation is determined by the stereoselective axial protonation of the cyclohexenyl bond in 6, or by the distribution of cyclohexene and cyclohexane conformers in 7 and 8, respectively. In the cases studied, it is clear that conformational inversion of the six-membered ring is slower than cyclization and thus ensures that an equatorial side chain leads to a trans A/B ring junction in the cyclization product, whereas an axial side chain affords a cis A/B ring junction.

AbstractAcid‐mediated cyclisation of trienone 8, readily available from 2,3‐dimethylbutanal (1; five steps: 47% yield), using fluorosulfonic acid (6.8 mol‐equiv.) in 2‐nitropropane at −70°, afforded a 14:9:1 mixture (70% yield) of (±)‐cis‐α‐irone (9), (±)‐trans‐α‐irone (10), and (±)‐β‐irone (11). Other acidic conditions examined, using 95% aq. H2SO4 solution, 85% aq. H3PO4 solution, or SnCl4, gave inferior results.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Acid-mediated cyclisation of trienone 8, readily available from 2,3-dimethylbutanal (1; five steps: 47% yield), using fluorosulfonic acid (6-8 mol-equiv.) in 2-nitropropane at -70-degrees, afforded a 14:9:1 mixture (70% yield) of (+/-)-cis-alpha-irone (9), (+/-)-trans-alpha-irone (10), and (+/-)-beta-irone (11). Other acidic conditions examined, using 95% aq. H2SO4 solution, 85% aq. H3PO4 solution, or SnCl4, gave inferior results.

Naturally occurring (-)-(R,R)-alpha-necrodol ((-)-1) and its C(4)-epimer (-)-2 are obtained in 84 and 44% yields, respectively, by lithium ethylenediamide (LEDA) treatment of the corresponding beta-necrodols (-)-3 and (-)-4 (Scheme 1, Table), both readily available from (-)-campholenyl acetate ((-)-i) by an efficient stereoselective synthesis. The thermodynamically preferred (-)-(R)-gamma-necrodol ((-)-5) becomes the major product (greater-than-or-equal-to 80% yield) after either prolonged treatment with LEDA or exposure of alpha- and beta-necrodols to BF3.Et2O. In an alternative route, (+)-5 is prepared starting from (+)-campholenal ((+)-ii) via Pd-catalysed decarbonylation to (-)-(S)-1,4,5,5-tetramethylcyclopent-1-ene ((-)-6) and subsequent application of an acid-catalysed CH2O-addition/rearrangement sequence (Scheme 2).

AbstractThe readily accessible monoterpenoid (R)‐(I) is used for the synthesis of the title compounds (R)‐(III) and (R)‐(VI), while their antipodes are prepared from (S)‐(I) by analogous routes.

Abstract(‐)‐(R)‐Campholenyl acetate (I) is the starting compound for the synthesis of two stereoisomers (+)‐(VIa) and (+)‐(VIb) of (‐)‐(R,R)‐β‐necrodol (‐)‐(VIa) which in turn can be obtained starting from (+)‐(VIb) via the intermediates (VII) and (VIII).

AbstractApplication of a stereoselective Prins/retro‐Prins rearrangement sequence from (−)‐(R)‐campholenyl acetate((−)‐4) opens a new access to the naturally occurring (−)‐(R, R)‐β‐necrodol ((−)‐1) and its three stereoisomers with high optical purity.

AbstractThe mixture of isomeric dimethyl‐endo‐tricyclo[5.2.1.02,6]deca‐3,8‐dienes (A) resulting from Diels‐Alder reactions of 1‐, 2‐, and 5‐methylcyclopenta‐1,3‐dienes (i–iii, respectively) at 20° was shown by GLC analysis to consist of at least 10 components (Table 1). The structures of the six major isomers 1–6, representing 96% of the total mixture, were established by 1H‐ and 13C‐NMR spectroscopy. Whereas on heating up to 110° the proportions of 1, 2, 4, and 6 remain nearly unaffected (±2 %), the dimers 3 and 5, formed in 22 % and 24 % yield, respectively, at 20°, isomerise above 70° reversibly via [3,3]‐sigmatropic rearrangement and equilibrate at 110° to a ca. 10:1 ratio.

AbstractThe transformation of 36 bis(homoallylic) alcohols VII to alkenones IX and X via β‐cleavage of their potassium alkoxides VIIa in HMPA has been investigated (cf. Scheme 2). These studies have established an order of β‐cleavage for 2‐propenyl, 1‐methyl‐2propenyl, 2‐methyl‐2‐propenyl, 1,1‐dimethyl‐2propenyl, and benzyl groups in alkoxides 49a–56a and have allowed a comparison between the β‐cleavege reaction and the oxy‐Cope rearrangement in alkoxides 74a–83a. As illustrative syntheti applications, a two‐step preparatio of propenyl ketones 15–42 from carboxylic esters is described, together with syntheses of ar‐turmerone (48), α‐damascone ((E)‐71), β‐damascone ((E)‐109), and β‐damascenone ((E)‐111).

AbstractThe bis(homoallylic) alcohols (III) are prepared from the respective lactones (I) and Grignard compounds (II) which are generated in situ.

AbstractStarting from γ‐ and δ‐lactones 1–3, a two‐step preparation of 3‐hydroxypropyl and 4‐ hydroxybutyl propenyl ketones 10–18 is described, involving as the key step the β‐cleavage of the bis(homoallylic) potassium alkoxides 4a–9a. The novel methodology is illustrated by a short synthesis of (±)‐rose oxide(20).

AbstractTreatment of the title compounds with either H3PO4 or BF3 · Et2O affords the bridged tricyclic lactones 3 and 7 as main products (57 and 70% yield, resp.). This is an efficient and novel access to specifically functionalised molecules possesing the bicyclo[3.2.1]octane skeleton. Lactones 4 and 5 and the bicyclic ketone 6 were formed as by‐products (2, 7, and 10% yield, resp.).