Thermal Cope Rearrangement Research Articles

Diastereoselective Synthesis of 2,3,4-Trisubstituted Tetrahydrofurans via Thermally Reactive 1,5-Diene-tert-butyl Carbonates

We report that 3,3-dicyano-1,5-dienes bearing tert-butyl carbonates can be thermally converted to 2,3,4-trisubstituted tetrahydrofurans. The transformation relies on two thermally reactive functional groups, a 1,5-diene and a tert-butyl carbonate, that react cooperatively to yield the furan scaffolds by thermal Cope rearrangement, Boc deprotection, and oxy-Michael addition. Described herein is background related to the discovery, optimization, and scope of the key transformation and representative functional group interconversion chemistry for the tetrahydrofuran scaffolds.

Synthesis of fused tricyclic systems by thermal Cope rearrangement of furan-substituted vinyl cyclopropanes.

A novel method for the stereoselective construction of hexahydroazuleno[4,5-b]furans from simple precursors has been developed. The route involves the use of our recently developed Brønsted acid catalysed cyclisation reaction of acyclic ynenones to prepare fused 1-furanyl-2-alkenylcyclopropanes that undergo highly stereoselective thermal Cope rearrangement to produce fused tricyclic products. Substrates possessing an E-alkene undergo smooth Cope rearrangement at 40 °C, whereas the corresponding Z-isomers do not react at this temperature. Computational studies have been performed to explain the difference in behaviour of the E- and Z-isomers in the Cope rearrangement reaction. The hexahydroazuleno[4,5-b]furans produced by Cope rearrangement have potential as advanced intermediates for the synthesis of members of the guaianolide family of natural products.

The Cope rearrangement of gem-dimethyl substituted divinylcyclopropanes

The reactivity of a range of substituted divinylcyclopropanes towards the thermal Cope rearrangement has been examined. The effects of gem-dimethyl substitution on the cyclopropane, the alkene geometry, the relative stereochemistry of the cyclopropane and the steric and electronic effects of a range of functional groups were all examined, and the methods developed were used to synthesise a range of functionalised 1,4-cycloheptadienes in high yields.

Photochemical generation of benzene–naphthalene biplanemers

A direct biplanemer synthesis could be achieved by a quantitative [4π+4π]photocycloaddition of benzyloxy substituted benzene and naphthalene rings ( 3d, e ⇄ 4d, e ). Since the products do not show a thermal Cope rearrangement—in contrast to the related longicyclic conjugated 9,10-benzotricyclo[4.2.2.2 2,5]dodeca-3,7,9-trienes—but a quantitative reverse reaction, they are interesting systems for an optical switching.

Germacrene A is a product of the aristolochene synthase-mediated conversion of farnesylpyrophosphate to aristolochene.

The biosynthesis of several sesquiterpenes has been proposed to proceed via germacrene A. However, to date, the production of germacrene A has not been proven directly for any of the sesquiterpene synthases for which it was postulated as an intermediate. We demonstrate here for the first time that significant amounts of germacrene A (7.5% of the total amount of products) are indeed released from wild-type aristolochene synthase (AS) from Penicillium roqueforti. Germacrene A was identified through direct GC-MS comparison to an authentic sample and through production of beta-elemene in a thermal Cope rearrangement. AS also produced a small amount of valencene through deprotonation of C6 rather than C8 in the final step of the reaction. On the basis of the X-ray structure of AS, Tyr 92 was postulated to be the active-site acid responsible for protonation of germacrene A (Caruthers, J. M.; Kang, I.; Rynkiewicz, M. J.; Cane, D. E.; Christianson, D. W. J. Biol. Chem. 2000, 275, 25533-25539). The CD spectra of a mutant protein, ASY92F, in which Tyr 92 was replaced by Phe, and of AS were very similar. ASY92F was approximately 0.1% as active as nonmutated recombinant AS. The steady-state kinetic parameters were measured as 0.138 min(-1) and 0.189 mM for k(cat) and K(M), respectively. Similar to a mutant protein of 5-epi-aristolochene (Rising, K. A.; Starks, C. M.; Noel, J. P.; Chappell, J. J. Am. Chem. Soc. 2000, 122, 1861-1866), the mutant released significant amounts of germacrene A (approximately 29%). ASY92F also produced various amounts of a further five hydrocarbons of molecular weight 204, valencene, beta-(E)-farnesene, alpha- and beta-selinene, and selina-4,11-diene.

The kinetically-controlled Cope rearrangement of 2,5-bis(4-methoxyphenyl)hexa-1,5-dienes induced by photosensitised electron transfer

H. Ikeda, A. Ishida, T. Takasaki, S. Tojo, S. Takamuku and T. Miyashi, J. Chem. Soc., Perkin Trans. 2, 1997, 849 DOI: 10.1039/A701043E

Some photochemical rearrangements of vinylcyclopentadienes. Mechanistic and exploratory organic photochemistry

The photochemistry of 2,3-diphenyl-1,4,5-trimethyl-5-vinylcyclopentadiene and 1,2-diphenyl-3,4,5-trimethyl-5-vinylcyclopentadiene was studied. The triplet of the 2,3-diphenyl isomer was found to undergo a 1,5-vinyl migration; in contrast, the 1,2-diphenyl diene was unreactive. On direct irradiation, in addition to vinyl migration, four photoproducts were formed from the cyclopentadienes. These were shown to be 5,6-diphenyl-1,2,7-trimethylbicyclo[3.2.0]hepta-2,6-diene, 1,5-diphenyl-2,6,7-trimethylbicyclo[3.2.0]hepta-2,6-diene, 6,7-diphenyl-1,2,5-trimethylbicyclo[3.2.0]hepta-2,6-diene, and 1,7-diphenyl-2,5,6-trimethylbicyclo[3.2.0]hepta-2,6-diene. A number of experimental observations led to a mechanism involving: (a) electrocyclic closure of the vinylcyclopentadienes to give vinyl housenes, (b) bicycling which interconverts isomeric housenes, and (c) thermal Cope rearrangement of the vinyl housenes to afford bicyclo[3.2.0]hepta-2,6-dienes. In addition, evidence was adduced for 1,5-vinyl shifts occurring in the vinylcyclopentadiene reactants.

On the mechanism of the thermal Cope rearrangement of allyl-substituted cyclopropenes

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the mechanism of the thermal Cope rearrangement of allyl-substituted cyclopropenesAlbert Padwa and Thomas J. BlacklockCite this: J. Am. Chem. Soc. 1978, 100, 4, 1321–1323Publication Date (Print):February 1, 1978Publication History Published online1 May 2002Published inissue 1 February 1978https://doi.org/10.1021/ja00472a064RIGHTS & PERMISSIONSArticle Views59Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (366 KB) Get e-Alerts Get e-Alerts

Demonstration of lack of inversion of the migrating allyl group in photochemical rearrangement of a hexa-1,5-diene derivative

UV irradiation of trans-2-(3′-deuterioallyl)cyclohexylidenemalononitrile (XIa) induces rearrangement to allyl-1-cyclohexenylmalononitrile, in which the deuterium is still entirely at the 3-position of the allyl group but has lost its geometrical configuration (XIIa and b). Thermal Cope rearrangement of the mixture (XIIa and b) or of pure synthetic cis-isomer (XIIa) forms 2-(1′-deuterioallyl)cyclohexylidenemalononitrile (XIb). Since XIa recovered from incomplete irradiation is quite unchanged and the cis-isomer (XIIa) is stable to irradiation even in the presence of cyclohexylidenemalononitrile, the cis-trans equilibration must occur during the migration of the allyl group.