- Platinum- and gold-catalyzed rearrangement reactions of propargyl acetates: Total syntheses of (-)-α-cubebene, (-)-cubebol, sesquicarene and related terpenes
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Propargyl acetates, in the presence of catalytic amounts of late transition-metal salts such as PtCl2 or AuCl3, represent synthetic equivalents of α-diazoketones. This notion is corroborated by a concise approach to various sesquiterpene natural products starting from readily available substrates. Specifically, (+)-carvomenthone (17) is converted into propargyl acetate (S)-26 by a sequence involving Stille cross-coupling of its kinetic enol triflate 18, regioselective hydroboration/oxidation of the resulting 1,3-diene 19, and addition of an alkynyl cerium reagent to aldehyde 21 thus obtained. Since the latter step was found to be unselective, the configuration of the reacting propargyl acetate was unambiguously set by oxidation followed by diastereoselective transfer hydrogenation by using Noyori's catalyst 25. Compound (5)-26, on treatment with PtCl2 in toluene, converted exclusively to the tricyclic enol acetate 27, which was sap onified to give norcubebone 11 in excellent overall yield. The conversion of this compound into the sesquiterpene alcohol (-)-cubebol (6) was best achieved with MeCeCl2 as the nucleophile, whereas the formation-of the parent hydrocarbon (-)-α-cubebene (4) was effected in excellent yield by recourse to iron-catalyzed cross coupling methodology developed in this laboratory. Since norketone 11 has previously been transformed into (-)-β-cubebene (5) as well as (-)-4-epicubebol 8, our approach constitutes formal total syntheses of these additional natural products as well. Along similar lines, the readily available propargyl acetates 1, 33 and 47 were shown to give access to 2-carene 44, sesquicarene 39, and episesquicarene 51 in excellent overall yields. In this series, however, the cy cloisomerization reaction was best achieved with catalytic amounts of AuCl3 in 1,2-dichloroethane as the solvent. In addition to these preparative results, our data provide some insight into the mechanism of these remarkable skeletal rearrangement reactions. Transformations of this type are likely triggered by initial coordination of the alkyne unit of the substrate to the carbophilic transition-metal cation. Formal attack of the alkene moiety onto the resulting π-complex engenders the formation of an electrophilic cyclopropyl carbene species which subsequently reacts with the adjacent acetate unit to give the final product. The alternative phasing of events, implying initial attack of the acetate (rather than the alkene moiety) onto the metal-alkyne complex, is inconsistent with the stereochemioal data obtained during this total synthesis campaign.
- Fuerstner, Alois,Hannen, Peter
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p. 3006 - 3019
(2008/02/04)
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- METHODS AND INTERMEDIATES FOR THE SYNTHESIS OF DELTA-9 TETRAHYDROCANNABINOL
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Processes are disclosed for the synthesis of Delta-9 tetrahydrocannabinol which result in an improved Y-THC/Y-THC ratio, and intermediates are disclosed that may be used in the synthesis of Delta-9 tetrahydrocannabinol such that improved Y-THCIY-THC ratios are achieved. The intermediates may be cyclic compounds prepared from 2-Carene. There is also provided a scaleable process for the preparation of (+)-p-menth-2-ene-1, 8-diol,, another intermediate used in the synthesis of delta-9-tetrahydrocannibinol.
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Page/Page column 3/7
(2008/06/13)
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- Intramolecular cyclopropanation reactions of organozinc carbenoids derived from terpenoid enals
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Treatment of a series of unsaturated terpenoid enals with 1,2 bis (chlorodimethylsilyl) ethane and zinc provides a simple and efficient method for intramolecular cyclopropanation.
- Motherwell, William B.,Roberts
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p. 1121 - 1124
(2007/10/02)
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- Chiral Synthesis via Organoboranes. 35. Simple Procedures for the Efficient Recycling of the Terpenyl Chiral Auxiliaries and Convenient Isolation of the Homoallylic Alcohols in Asymmetric Allyl- and Crotylboration of Aldehydes
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Asymmetric allyl- and crotylboration of aldehydes, RCHO, with terpenyl-based allyl- and crotylborane reagents Ter2*BAll (1), Ter2*BCrtZ (2), and Ter2*BCrtE (3, Ter* = Ipc, 4-Icr and 2-Icr; All = allyl and Crt = crotyl), afford Ter2*BOCH*(R)C*(1R)(2R)CH=CH2 intermediates 4.In these reactions, the isolation of homoallylic alcohols, HOCH*(R)C*(1R)(2R)CH=CH2 (5), can be accomplished via oxidation of 4 with alkaline hydrogen peroxide.Unfortunately, oxidative workup destroys the chiral auxiliary and produces a large amount of nonrecyclable byproduct, terpenol (Ter*OH).Further, isolation of the pure homoallylic alcohol by distillation can be difficult if it boils in the range of the abundant byproduct.Therefore, in order to recycle the chiral auxiliaries and isolate the product homoallylic alcohols in an efficient manner, we have developed the following procedures: (1) elimination workup, in which enantiomerically pure α-pinene and Δ2- and Δ3-carenes are liberated from terpenylborinates 4 by treatment with isobutyraldehyde and 1 mol percent BF3*OEt2; (2) ethanolamine workup involving treatment of 4 with ethanolamine (EA) to achieve the precipitation of the ethanolamine adducts (EA-BTer2*, Ter* = Ipc and 2-Icr, 11 and 12) from which the Ter2*BOMe can be easily regenerated; and (3) 8-hydroxyquinoline workup, involving treatment of 4 with 8-hydroxyquinoline (8-HQ) to precipitate the 8-HQ adducts (8-HQ-BTer2*, Ter* = Ipc, 4-Icr and 2-Icr, 13-15), from which the various Ter2*BOMe intermediates can be conveniently liberated.It is hoped that these procedures will significantly enhance the scope of asymmetric allyl-/crotylboration of aldehydes with Ter2*BAll (1), Ter2*BCrtZ (2), and Ter2*BCrtE (3) and serve as excellent alternatives for any catalytic versions yet to be discovered.
- Brown, Herbert C.,Racherla, Uday S.,Liao, Y.,Khanna, Vijay V.
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p. 6608 - 6614
(2007/10/02)
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- Stereospecific Conversions of (+)-2- and (+)-3-Carenes into Optically active Seven-Membered Ring Systems
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The reactions of (+)-2-carene (6b) and (+)-3-carene (15) with iron carbonyls are studied under various conditions.Besides double bond isomerization and interconversion of the two isomeric hydrocarbons, at least two different modes of ring opening leading to six- and seven-membered ring products are observed.Under mild conditions the primary ring opening complex 7b is isolated without loss of sterical information.Carbonylation of 7b under various conditions yields optically active cycloheptene systems 18, 19, and 20 or the bicyclic systems 9b and 10b.
- Eilbracht, Peter,Winkels, Irmgard
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p. 191 - 198
(2007/10/02)
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- Acid-catalysed Terpenylations of Olivetol in the Synthesis of Cannabinoids
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Examination of the toluene-p-sulphonic acid-catalysed reaction of (1S,2S,3R,6R)-(+)-trans-car-2-ene epoxide with olivetol shows that, inconsistently with the accepted mechanism, (3R,4R)-(-)-o- and -p-cannabidiols are produced as well as (3R,4R)-(-)-Δ1- and Δ6-tetrahydrocannabinols.Evidence is now presented that, as in Petrzilka's reaction employing chiral p-mentha-2,8-dien-1-ols, the reacting species is the delocalised (4R)-p-mentha-2,8-dien-1-yl cation (9).Similar terpenylation using (1S,3S,4R,6R)-(+)-trans-car-3-ene epoxide shows that besides the reported (-)-Δ6-THC, o- and p-cannabidiols, Δ1-THC and Δ4,8-iso-THC can also be produced.The nature of the products, the chirality, and the characteristics of the reaction implicate again the delocalised cation (9).Its formation via Kropp-type rearrangement is excluded and a pathway leading to (4R)-p-mentha-2,6,8-triene, which on protonation gives (9), is proposed.Protonated on C-8, the triene can be trapped and isolated as (4R)-p-mentha-2,6-dien-8-ol.The latter, made in (+/-)-form from citral, proved to be an excellent terpenylating agent for producing cannabinoids.Terpenylation of olivetol by the pinanes (1S,4S,5S)-(-)-cis-verbenol and (1R,5S,7R)-(+)-cis-chrysanthenol is compared.A major drawback of the latter is partial racemisation which occurs in the verbenone-chrysanthenone isomerisation during its photochemical preparation.Whilst Δ1-THC cannot be directly obtained from verbenol, its tertiary allylic cation permits a much higher yielding terpenylation than the secondary cation from chrysanthenol.
- Crombie, Leslie,Crombie, W. Mary L.,Jamieson, Sally V.,Palmer, Christopher J.
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p. 1243 - 1250
(2007/10/02)
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- CYCLOPROPANE FORMATION FROM 4,5-UNSATURATED THIOPHENYLETHERS. CONVERSION OF LIMONENE INTO CAR-2-ENE
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Strong bases can abstract a proton α to a double bond.A phenylthio group γ to that double bond can be eliminated at the same time leading to a cyclopropane ring.The procedure is illustrated by a conversion of limonene into car-2-ene.
- Fourneron, J. D.,Harwood, L. M.,Julia, M.
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p. 693 - 696
(2007/10/02)
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