Claisen rearrangement, mechanism

In an imioortant industrial process, the Carroll reaction , an ahphatic version of the Claisen rearrangement occurs. See if you can find the right mechanism ... 

Conversion of 5-allylthioimidates into /V-allylthioamides is catalyzed by Pd(Il). 2-Allylthiopyridine (820) is converted into the less stable l-allyl-2-thio-pyridone 821 owing to Pd complex formation[509], Claisen rearrangement of 2-(allylthio)pyrimidin-4-(3//)-one (822) affords the A-l-allylation product 823 as the main product rather than the A -3-allylation product 824[510] The smooth rearrangement of the allylic thionobenzoate 825 to the allyl thiolo-benzoate 826 is catalyzed by both PdCl2(PhCN)2 and Pd(Ph3P)4 by different mechanisms[511],... 

Q The mechanism of the Claisen rearrangement of other allylic ethers of phenol is analogous to that of allyl phenyl ether What is the product of the Claisen rearrangement of C6H50CH2CH CHCH3 /... 

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). 

Active Figure 18.1 The mechanism of the Claisen rearrangement. The C—0 bond-breaking and C—C bond-making occur simultaneously. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Because of the nature of the transition state in the pericyclic mechanism, optically active substrates with a chiral carbon at C-3 or C-4 transfer the chirality to the product, making this an enantioselective synthesis (see p. 1451 for an example in the mechanistically similar Claisen rearrangement). ... 

Evidence is the lack of a catalyst, the fact that the reaction is first order in the ether, the absence of crossover products when mixtures are heated, and the presence of the ally lie shift, which is required by this mechanism. A retro-Claisen rearrangement is... 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

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]. 

Claisen rearrangement. As for the mechanism, the reaction begins with intramolecular cyclopropanation the resulting bicyclo[2.1.0]pentan-2-one then undergoes fragmentation to a p,y-unsaturated ketene which finally is trapped by the added alcohol to afford a p,y-unsaturated ester (Scheme 41). The intermediates could be observed in selected cases. 

Chorismate mutase catalyzes the Claisen rearrangement of chorismate to prephenate at a rate 106 times greater than that in solution (Fig. 5.5). This enzyme reaction has attracted the attention of computational (bio)chemists, because it is a rare example of an enzyme-catalyzed pericyclic reaction. Several research groups have studied the mechanism of this enzyme by use of QM/MM methods [76-78], It has also been studied with the effective fragment potential (EFP) method [79, 80]. In this method the chemically active part of an enzyme is treated by use of the ab initio QM method and the rest of the system (protein environment) by effective fragment potentials. These potentials account... 

Important advances in propargylic etherification have come from the use of copper-based systems that achieve efficient, catalytic O-progargylation of phenols (Scheme 8).245,246 While the mechanism of this transformation remains unclear, the products of these reactions have been readily converted into chromenes through subsequent Claisen rearrangement,... 

Scheme 4.53. Proposed mechanism of a zinca-Claisen rearrangement...

The Claisen rearrangement is an electrocyclic reaction which converts an allyl vinyl ether into a y,8-unsaturated aldehyde or ketone, via a (3.3) sigmatropic shift. The rate of this reaction can be largely increased in polar solvents. Several works have addressed the study of the reaction mechanism and the electronic structure of the transition state (TS) by examining substituent and solvent effects on the rate of this reaction. 

So basically the Claisen rearrangement is a thermal [3, 3] sigmatropic rearrangement of allyl vinyl ether. The mechanism is probably as follows ... 

The conversion of [49] into [50] involves a Claisen rearrangement. Once this was realized it was less surprising that no specific catalytic groups on the enzyme are involved. Support for the Claisen-type mechanism comes from the inhibition shown by the bicyclic dicarboxylate [51], prepared by Bartlett and Johnson (1985) as an analogue of the presumed transition state [52], This same structure [51], coupled through the hydroxyl group to a small protein, was used as a hapten to induce antibodies, one (out of eight) of which mimics the behaviour of chorismate mutase, albeit less efficiently (Table 7). 

Various mechanisms are discussed for the migration of a benzyl group including, e.g., a two-stage Cope or reverse Claisen rearrangement as well as a preference of direct [l,5]-shift over successive Wagner-Meerwein migrations (equation 115)173. 

The third mechanism starts with addition of the AT-allylamine 103 to the cumulated acceptor system of an allene carbonester 108 (Acc=CHC02Me) to form an intermediate iV-allyl ammonium amide enolate 109 (allene carbonester Claisen rearrangement). The anion stabilizing group is exclusively placed... 

These ideas will be discussed in the following subsections, where most of the attention will be devoted to the mechanistic smdies with aromatic esters, which have been the subject of an overwhelming majority of the research efforts. Nevertheless, the same reaction mechanism has been shown to be valid for the PFR of anilides, thioesters, sulfonates, and so forth. Furthermore, it is also applicable to the photo-Claisen rearrangement [i.e. the migration of alkyl (or allyl, benzyl, aryl,)] groups of aromatic ethers to the ortho and para positions of the aromatic ring [21,22]. 

---