Cope-Claisen rearrangement

Bicyclic ketone (33) was needed for a chrysanthemic acid synthesis. tarbene disconnection next to the ketone group (Chapter T30) reveals y. (5-unsaturated acid (35) as an intermediate, available by a Claisen-Cope rearrangement. 

Cairns N, Harwood LM, Astles DP (1994) Tandem thermal claisen-cope rearrangements of coumarate derivatives. Total syntheses of the naturally occurring coumarins suberosin, demethylsuberosin, ostruthin, balsamiferone and gravelliferone. J Chem Soc Perkin Trans... 

CLAB underground spent fuel disposal facility, 17 549 Cladinose, 4 713 Claflin refiner, 15 105 CLAIMS-Citation database, 15 238 CLAIMS-Citation files, 15 247, 248 CLAIMS Compound Registry, 15 247 CLAIMS databases, 15 237, 247 Claisen condensation, 10 505 Claisen-Cope rearrangement, 24 479,... 

Claisen-Cope rearrangement of the allyl vinyl ether. The ether (1.1 g) is heated for 30 minutes at 180-185 °C under nitrogen in a fully immersed half-filled sealed Pyrex glass tube (CAUTION). After cooling, the product is distilled under reduced pressure to furnish 4-(4-methylphenyl)pent-4-enal (850 mg, 87%), b.p. 100-102 °C/5-7mmHg i.r. (film) 2700, 1710 (CHO), 3070, 1650, 890 (>C=CH2), and 825cm-1 (para-substituted benzene). 

It was later found that the same sort of reaction occurs without the aromatic ring. This is called either the aliphatic Claisen rearrangement or the Claisen-Cope rearrangement. Here is the simplest possible example. 

Orbital symmetry tells us that [3,3]-sigmatropic rearrangements are allowed but says nothing about which way they will go. They are allowed in either direction. So why does the Claisen-Cope rearrangement always go in this direction ... 

The application of consecutive rearrangements to aliphatic systems has been exceptionally rewarding. A seminal contribution is provided by the work of Thomas, who has prepared p-sinesal (26 equation 7), a constituent of the essential oil of the Chinese orange, by the tandem Claisen-Cope rearrangement. ... 

Because the Cope rearrangement is an equilibrium driven reaction, the application of the Claisen-Cope rearrangement to synthesis requires the target substrates to be more stable than their Cope precursors. Thus, in the instance of equation (8), the 1,5-hexadienes (30) and (34) bear a monosubstituted and a 1,1-disubstituted double bond, which are less stable than the trisubstituted double bonds of p-sinesal. 

When the Claisen-Cope rearrangement is applied to (-)-ci5-carveol (54 Scheme 3) at 100 °C, a dextrorotatory mixture of aldehydes (55) is isolated after the initial Claisen rearrangement, in addition to small amounts of the Claisen-Cope ( )-unsaturated aldehyde (57) ([ajo = -5 ) and its (2)-isomer. Thermolysis of (55) at 150 C gives aldehyde (57) ([a]o = -8.4 ) and at 400 C the product displays no rotation. At elevated temperature the reaction presumably occurs via a diradical species as the rotation of ent- Sl), prepared via (56) from (54), is [a]o = -(-12. ... 

The success of the Claisen-Cope rearrangement need not be limited to the production of aldehydes via enol ethers. Allylic alcohol (58) is successively transposed into a mixture of allylic isomers (59 Scheme 4), and is subjected to an orthoester Claisen rearrangement at 150 "C to provide ester (61). The moderate temperature of the Claisen step permits the isolation of an intermediate (c/. Scheme 3) prior to the final Cope rearrangement (195 C) to. y-unsaturated esters (60). The esters (60) are a 55 45 mixture of ( )- and (Z)-double bond isomers owing to the near equal steric bulk of the methyl and acetic acid residues in the transition state for the Cope rearrangement. ... 

Two other examples of carbanion -accelerated rearrangements have been described in the literature. The first one leads from the anion of the 60-allylic guanine 211 in two consecutive [3.3] sigmatropic shifts (a combined Claisen-Cope rearrangement) via 212 and 213 to the 8-allylic guanine 214 173). 

Thomas and Ozainne" have explored the tandem Claisen-Cope rearrangement on aromatic substrates. Treatment of 2-furfuryl alcohol with diene (25 equation 9) provides a 9 1 mixture of Claisen-Cope product (39) and furan (37), respectively. The minor component arises via the forbidden [1,3] prototropic shift of the initial Claisen intermediate (38), thereby reestablishing the aromaticity of the furan ring. 

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