The Claisen-Cope rearrangement

As a means of transferring the site of asymmetry the Claisen-Cope rearrangement is without comparison. Thus in the rearrangement of allyl vinyl ether (123) the original stereogenic centre is destroyed but two new centres are formed with retention of the overall chirality of the molecule to give (124).(53] 

The rearrangement can be adapted to give a second-generation asymmetric synthesis by rendering the faces of one or other double bond diastereotopic as in (125) with a chiral auxiliary derived from (S)-valine.[5 14-Pentenoic acids (126) substituted at C-2 are available in high e.e. by this method. 

Like so many 6-electron concerted reactions, the Claisen-Cope rearrangement prefers to pass through a chair-like transition state (127), which explains its great predictability. The extension to 3-substituted pentenoates (128) is straightforward.I S] 

For an account of an asynunetric ene reaction somewhat analogous to this example, see section 7.2.5. 

Greuter, J. Dingwall, P. Martin and D. Bellus, Helv. Chim. Acta, 1981,64,2812. 

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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 ... 

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. ... 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

The Claisen-Cope rearrangement is much easier to use. The starting material is an allyl vinyl ether 149 that can be made from an allylic alcohol. The product looks as though it might have been made by the allylation of an enol(ate) and the same disconnection 150 does for both. In this simple case, the product could equally well be made from an enamine of acetaldehyde and allyl bromide but you should by now realise that more complicated examples need a lot of control. 

This is true also of allylic esters 182 so that the geometry of both alkenes involved in the Claisen-Cope rearrangement can be controlled if the lithium enolate is trapped by silylation to give 183. Drawing the rearrangement in the chair conformation 183a — 184 gives a predictable diastereoisomer of the product 185. 

The scope of the Claisen-Cope rearrangement is very great but you have been given enough mechanistic and stereochemical detail to unravel all but the most difficult. The disconnection is always simple - the reaction corresponds to an allylation of an enolate and, providing you remember to turn the allylic system inside out, you will find the starting materials. All that remains is to identify which method to use and how to control the stereochemistry. Oh, and you also have to make the starting materials ... 

In a continuation of their studies on the Claisen-Cope rearrangement, Thomas etal have utilised this procedure in the synthesis of torreyaland dendro-lasin. Thus, pyrolysis of the ether (20), derived from the reaction of 3-furyl-methanol with l-ethoxy-2-methylbuta-1,3-diene, gave the aldehyde (21). This, on reduction to the corresponding alcohol and further treatment with the above diene, yielded torreyal (22, R = CHO) which could be converted to dendrolasin... 

The Claisen-Cope rearrangement of ( — )-ew-carveol (69) with vinyl ether 59 affords theClaisen product ( + )-70 and small amounts of Claisen-Cope product 71 and its (Z)-isomer. Conversion of 70 is achieved by heating to 150°C396. 

The dimerisation to give (10) is usually a nuisance but it does make (10) readily available. The Claisen-Cope rearrangement goes from (9) to (6) because a carbonyl group is formed at the expense of a less stable C=C double bond. 

FIRST- AND SECOND-GENERATION METHODS 5.5.2 The Claisen-Cope rearrangement... 

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