Claisen Rearrangement Reactions

Like the Diels-Alder reaction discussed in Sections 14.4 and 14.5, the Claisen rearrangement reaction takes place through a pericyclic mechanism in which a concerted reorganization of bonding electrons occurs through a six-membered, cyclic transition state. The 6-allyl-2,4-cyclohexadienone intermediate then isomerizes to o-allylpbenol (Figure 18.1). 

Claisen rearrangement reaction (Sections 18.4, 30.8) The pericyclic conversion of an allyl phenyl ether to an o-allylphenol by heating. 

Asymmetric Claisen rearrangement reactions are well known. Chiral Lewis... 

Due to the AV (volume change of activation) of Claisen rearrangements having a negative value, as in the Diels-Alder reactions, the Claisen rearrangement reaction is expected to be accelerated by water according to the same effect.151,152... 

In this contribution, we describe work from our group in the development and application of alternatives that allow the explicit inclusion of environment effects while treating the most relevant part of the system with full quantum mechanics. The first methodology, dubbed MD/QM, was used for the study of the electronic spectrum of prephenate dianion in solution [18] and later coupled to the Effective Fragment Potential (EFP) [19] to the study of the Claisen rearrangement reaction from chorismate to prephenate catalyzed by the chorismate mutase (CM) enzyme [20]. 

All Claisen Rearrangement reactions described to date require temperatures of> 100 °C if uncatalyzed. The observation that electron withdrawing groups at C-l of the vinyl moiety exert a positive influence on the reaction rate and the yield has led to the development of the following variations ... 

Although a chairlike transition state is favored for the Claisen rearrangement reactions of acyclic substrates, this is not always the case with cyclic systems. For example, Bartlett and Ireland independently studied the rearrangement reactions of cyclohexenyl silylketeneacetals and found that there was competition between the chairlike and boatlike transition states11 (Scheme l.VII). Clearly, the -isomer IE gives 8a via a chairlike transition state, whereas the Z-isomer 7Z affords the same product (8a) via a boatlike transition state. 

In accessing chiral allyl vinyl ethers for Claisen rearrangement reactions, Nelson et al. employed the iridium-mediated isomerization strategy. Thus, the requisite enantioenriched diallyl ether substrate 28 was synthesized via a highly enantioselective diethylzinc-aldehyde addition protocol10 (Scheme 1.1k). The enantioselective addition of Et2Zn to cinnamaldehyde catalyzed by (—)-3-exo-morpholinoisobomeol (MIB 26)11 provided an intermediate zinc alkoxide (27). Treatment of 27 with acetic acid followed by 0-allylation in the presence of palladium acetate delivered the 28 in 73% yield and 93% ee. Isomerization of 28 with a catalytic amount of the iridium complex afforded the allyl vinyl ether... 

Bourgeois, D., Craig, D., King, N.P., and Mountford, D.M. 2005. Synthesis of homoallyhc sulfones through a decarboxylative Claisen rearrangement reaction. Angewandte Chemie International Edition, 44 618-21. 

Craig, D. and Grellepois, F. 2005. Decarboxylative Claisen rearrangement reactions of allylic tosylmalonate esters. Organic Letters, 7 463-65. 

As mentioned for the Ireland-Claisen rearrangement, asymmetric Claisen rearrangement reactions are well known.Chiral Lewis acids have been designed for... 

Figure 2 (a) QM/MM energy profiles for the Claisen rearrangement reaction of... 

In order to acquire a set of spectral data allowing the assignment of configuration at C-24 and C-25 of 24-methyl-26-hydroxysteroids, model compounds with all possible configurations at C-24 and C-25 were synthesized by a scheme involving a Claisen rearrangement reaction on cA-allylic C-22 alcohols (80) (Fig. 20). These were converted, by reaction with triethyl-orthopropionate, into a... 

A few solvent-free examples of Claisen rearrangement reactions under the action of microwave irradiation have been described. One involves the double Claisen rearrangement of bis(4-allyloxyphenyl)sulfone into bis(3-allyl-4-hydroxy-phenyl)sulfone (Scheme 8.43) [111]. Similarly, 3 -allyl-2 -hydroxyacetophenone has been obtained in quantitative yield from 2 -allyloxyacetophenone by Bennett et al. [112]. 

Corey and Kania reported an enantioselective Claisen rearrangement reaction of macrocychc lactone for the synthesis of (-l-)-dollabellatrienone (56) [13], Reaction of the lactone 53 with chiral (5,5)-diazaborolidine L2BBr 54 and Barton s base (6) resulted in Claisen rearrangement to give carboxylic acid 55 in 86% yield with >98% ee (diastereos-electivity >98 2) (Scheme 7.10). In this reaction, rapid deprotonation by sterically hindered guanidine base is the key to suppress side reactions. 

Amauromine, a dimeric indole alkaloid with hypotensive vasodilator properties, was isolated from Amauroascus species (Gymnoascales, Ascomycotina) (267) and Penicillium verrucosum (26S). The structure of this metabolite was determined by chemical and spectroscopic investigations and confirmed by a total synthesis by Takase et aL 268). The symmetrical diketopiperazine made up of two modified tryptophans, each bearing a 1,1-dimethylallyl group at C-3, was synthesized as shown briefly in Scheme 45. The two inverted prenyl groups were introduced simultaneously by a thio-Claisen rearrangement reaction through the sulfonium salt. 

An interesting method of indole C-4 substitution has been developed from a Claisen rearrangement. Reaction of 3-hydroxy-2-methoxyindoline (349) with W,A(-dimethylacetamide dimethylacetal gives the intermediate (350), which undergoes a Claisen rearrangement to yield a mixture of the 4-substituted indoline (351) and indole (352). The indoline can be converted into the indole by a sequence of methanol ehmination and base hydrolysis (Scheme 111) <(90CC78i). 

APPLICATIONS OF THE CLAISEN REARRANGEMENT REACTION IN TARGET-ORIENTED SYNTHESIS... 

Scheme 13.30 Sequential Johnson-Claisen and Eschenmoser-Claisen rearrangements. Scheme 13.31 Double Ireland-Claisen rearrangement reactions.

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