Intramolecular Claisen reaction mechanism

Two possible mechanisms exist for the Friedlander reaction. The first involves initial imine formation followed by intramolecular Claisen condensation, while the second reverses the order of the steps. Evidence for both mechanisms has been found, both... 

The following reaction involves a conjugate addition reaction followed by an intramolecular Claisen condensation. Write both steps, and show their mechanisms. 

Intramolecular Claisen condensations, called Dieckmann condensations, are ringclosing reactions that yield 2-cyclopentanone carboxylic esters (Figure 10.52) or 2-cyclohexanone carboxylic esters. The mechanism of the Dieckmann condensation is, of course, identical to the mechanism of the Claisen condensation (Figure 10.51). To ensure that the Dieckmann condensation goes to completion, the presence of a stoichiometric amount of base is required. As before, the neutral /3-ketoester (B in Figure... 

BPS catalyzed the stepwise condensation of benzoyl-CoA with three molecules of malonyl-CoA to give a tetraketide intermediate that was cyclized by intramolecular Claisen condensation into 2,4,6-trihydroxybenzophenone (Figure 2). The enzyme was inactive with CoA-linked ciimamic acids such as 4-coumaroyl-CoA, the preferred starter substrate for chalcone synthase (CHS). BPS and CHS from H. androsaemum cell cultures shared 60.1% amino acid sequence identity. CHS is ubiquitous in higher plants and the prototype enzyme of the type III PKS superfamily (1,2). It uses the same reaction mechanism like BPS to form 2, 4,4, 6 -tetrahydroxychalcone, the precursor of flavonoids (Figure 2). 

Goering et al. reported asymmetric aromatic Claisen rearrangement by intramolecular chirality transfer related to the study on elucidation of reaction mechanism [62]. The thermal rearrangement of the E isomer of (J )-but-3-en-2-yl phenyl ether 69 proceeded at 200 °C to give a mixture of E isomer 70 and Z isomer 71 in a ratio of 82 18, although the optical purity of each product was not shown. 

The mechanism involves a Michael reaction followed by a Dieckmann reaction (intramolecular Claisen), all base promoted. Loss of the ester group begins with an add-catalyzed hydrolysis, followed by decarboxylation of the resulting carboxylic acid. Finally, a Robinson annulation with methyl vinyl ketone affords the final product. 

There are few mechanistic studies for the Dieckmann condensation. " The reaction can simply be described as an intramolecular Claisen condensation and hence entirely reversible. The summation of the consensus for its mechanism is as follows the reaction is initiated by anion formation through the abstraction of the most acidic proton on the a-carbon to one of the di-... 

Notice once again that the product is just a P-keto ester. This reaction has its own name (the Dieckmann condensation). But it is really just an intramolecular Claisen condensation. Therefore, the steps of this mechanism are identical to the steps of a regular Claisen condensation. Propose a mechanism for the Dieckmann condensation. Try to do it without looking back at your previous work. You will need a separate piece of paper to record your answer. 

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. 

Claisen rearrangement. The reaction is intramolecular and has a cyclic mechanism. 

The-Claisen rearrangement to the ortho position is a first-order reaction,67 68 and the process does not require catalysis by acids and bases. The rearrangement is intramolecular, since rearrangement of mixtures of ethers such as allyl /3-naphthyl ether and cinnamyl phenyl ether,60 or cinnamyl 4-methylphenyl ether and allyl 4-aminophenyl ether,68 yields none of the cross products which would result from an intermolecular reaction. The process is best represented by the cyclic mechanism, in which the following processes take place, with the electronic shifts during reaction indicated by the arrows.23 39 69... 

To most organic chemists the term Claisen condensation implies the self-condensation of esters in the presence of sodium ethoxide to give 0-ketoesters. A Dieckmann condensation is a special Claisen condensation in which an ester of a dibasic acid undergoes intramolecular condensation to produce a cyclic jS-ketoester. From the point of view of mechanism, however, this idea of a Claisen condensation is perhaps unnecessarily limited, for there are a number of extremely closely related reactions which involve compounds other than esters, and bases other than sodium ethoxide. In all these transformations, the essential feature of the reaction is the addition of a carbanion to a carbonyl group, followed by the loss of a negative ion from the seat of reaction. 

Claisen rearrangements are formally intramolecular processes that involve concomitant cr bonds breaking and the formation as well as migration of n bonds. On the other hand, numerous investigations support a more or less concerted mechanism for this type of reaction depending on the nature of substituents on the 1,5 diene unit [Id]. 

Just as there is an intramolecular version of the aldol condensation (see Section 22.2), there is an intramolecular version of the Claisen condensation. A simple illustration is treatment of an a,(0-diester such as diethyl 1,6-hexanedioate (77, the diethyl ester of adipic acid called diethyl adipate see Chapter 20, Section 20.9) with sodium ethoxide in refluxing ethanol. When this experiment is done, triphenylmethide (19 introduced in Section 22.1) is used as the base, and reaction in the solvent benzene gives the isolated flnal product (86) in 70% yield. Note that benzene is rarely used now-a-days because it is a suspected carcinogen and its use is being phased out. This reaction sequence uses the same mechanism as the Claisen condensation. 

When first reported by Cope and Hardy, similarities between this and the Claisen rearrangement were immediately recognized, and it was thus hypothesized that the reaction proceeds through a concerted, intramolecular, cyclic transition state. To confirm this mechanism, a series of experiments were conducted which strongly supported Cope s initial postulate. 

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