Claisen reaction mechanism

The mechanism for the Claisen reaction (Mechanism 24.4) resembles the mechanism of an aldol reaction in that it involves nucleophilic addition of an enolate to an electrophilic carbonyl group. Because esters have a leaving group on the carbonyl carbon, however, loss of a leaving group occurs to form the product of substitution, not addition. 

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

Problem 23.12 As shown in Figure 23.5, the Claisen reaction is reversible. That is, a /3-keto ester can be cleaved by base into two fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs. 

The initial reaction in Problem 29.42, conversion of two molecules of acetyl CoA to one molecule of acetoacetyl CoA, is a Claisen reaction. Assuming that there is a base present, show the mechanism of the reaction. 

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. 

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]. 

A zinca ene reaction is by definition (M. B. Smith and J. March, Advanced Organic Chemistry—Reactions, Mechanisms, and Structure, 5th edition, Wiley, New York, 2001, p. 1377) not a rearrangement, because it involves two different molecules. Nevertheless, reactions of the type described in equation 30 are included in this review regardless whether the authors rationalized them by a metallo-ene or metallo-Claisen pathway. This is justified since the original mechanistic assumptions were modified later (see Section II.A.3). 

A reaction mechanism quite similar to the Claisen-Tishchenko and Meerwein-Pondorf-Verley reactions assumes tetravalent aluminum in an anionic complex and is more likely to correspond to the requirements. 

The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues has provided acyclic alkynes bearing a 1,3-diketone-type moiety.19 The reaction mechanism has been proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate (Scheme 2). 

Chorismate mutase catalyses the Claisen rearrangement of chorismate to form prephenate. It is an excellent system for analysing catalysis because the same reaction occurs in solution with the same reaction mechanism no covalent catalysis by the... 

The final step is a retro-Claisen reaction, whose mechanism is pictured in Section 29.3 as Step 4 of (3-oxidation of fatty acids. 

These trajectories do provide a means for reconciling all of the data into a cohesive fi amework. The [2-1-2] and [2-1-4] prodncts can be formed from passage over the same TS. This explains why both products are observed even at short reaction times and precludes the necessity of the two-step ([4-1-2] followed by the Claisen rearrangement) mechanism. It obviates the requirement for climbing the very large barriers associated with the direct [2-1-2] pathways that were problematic when just examining the potential energy surfaces. Trajectory analysis allows for an interpretation of the KIEs. TST adequately accounts for the KIEs for Reaction 8.7. 

The mechanism of the Dieckmann reaction is exactly the same as the mechanism of an inter-molecular Claisen reaction. It is illustrated in Mechanism 24.5 for the formation of a six-membered ring. 

The rearrangement of modihed glycals provides novel strategies for the preparation of C-glycosides. Such reactions involve the sigmatropic mechanisms associated with both Cope and Claisen reactions. In this section, these reactions will be overviewed in the context of 3,3-sigmatropic rearrangements. 

The mechanism of the Dieckmann cyclization, shown in Figure 23.6 (p. 954), is analogous to that of the Claisen reaction. One of the two ester groups is converted into an enolate ion, which then carries out a nucleophilic acyl substitution on the second ester group at the other end of the molecule. A cyclic /S-keto ester product results. 

Dienone-phenol rearrangements are mechanistically diverse. They may involve 1,2-shifts of the Wag-ner-Meerwein type, or of the benzil-benzilic acid kind 1,3-shifts by a Claisen-Cope mechanism 1,5-sigmatropic shifts Favorskii-like reactions and other types. They may also be induced photochemically. A number of reviews are available, which discuss mechanistic aspects in detail. In this chapter emphasis is put on preparative aspects of these reactions and the examples are organized on a structural basis, stressing the new bond(s) formed. 

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). 

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