Dieckmann Condensation Reactions

Claisen condensation reaction Dieckmann cyclization Michael reaction Michael acceptor... 

Chemists have estabhshed that a Dieckmann condensation will not succeed unless the final keto-ester product is deprotonated by a base. In our example, this would be a reaction between EtO" and the keto-ester (it is necessary, therefore, to use excess EtO ). What reaction products are generated by this proton transfer Obtain the energies of the reactants and products, and calculate the energy for this final proton transfer. Is this reaction thermodynamically favorable or unfavorable Does this step make the overall condensation reaction favorable or unfavorable ... 

Carboxylic esters 1 that have an a-hydrogen can undergo a condensation reaction upon treatment with a strong base to yield a /3-keto ester 2. This reaction is called the Claisen ester condensation or acetoacetic ester condensation, the corresponding intramolecular reaction is called the Dieckmann condensation ... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

Dieckmann cyclization reaction (Section 23.9) An intramolecular Claisen condensation reaction to give a cyclic /3-keto ester. 

Scheme 5.6 Industrial Dieckmann condensation reaction (a), and a literature protocol (b) used in an educational laboratory. (A similar protocol is given in reference [30] (experiment 4023).) Of course, base and acid are not entered simultaneously.

Figure 5.9 Mass indices and environmental factors E for the Dieckmann condensation reactions depicted in Scheme 5.5, using the software EATOS Results for laboratory (L) (f 0.2 kg) and operation (O) (f l 500 kg) scale, as well as for a literature protocol (Lit.) (scale 0.01 2 kg ) are shown.

The use of classical condensation reactions is important. Thus, the Dieckmann reaction (equation 38) and the Thorpe-Ziegler cyclization (equation 39) have been used for almost a century for the preparation of a wide range of monocyclic and benzo-fused heterocycles. The aldol condensation and related reactions have also been fairly widely exploited, especially for the synthesis of 4-quinolones (the Camps reaction, e.g. equation 40), and various extensions of this general approach are described in the monograph chapters. 

A very useful method for generating 3 (2H)- dihydrofuranones is based on the Michael addition of anions derived from a-hydroxyesters to a,/3-unsaturated substrates (Scheme 82). The intermediate anion attacks the adjacent ester moiety via a Dieckmann condensation reaction to produce a substituted furanone ring which usually bears useful functionality. Overall yields of 45-60% have been obtained for this reaction. 

Intramolecular ester condensation reactions are called Dieckmann condensations and are very useful ring-forming reactions. Examples are shown in the following equations. In the second equation the yield is only 54% if sodium ethoxide is used as the base. 

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... 

Condensation reactions of the aldol type play an important part in heterocyclic chemistry. There are a large number of condensation reactions that are closely related to the aldol condensation. Each of these reactions has its own name Claisen, Dieckmann, Doebner, Knoevenagel, Perkin, to mention a few, but the chemistry is essentially the same as that of the aldol condensation. 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

The intramolecular condensation of ester enolates provides efficient access to 5- and 6-member ring P-keto esters. Similar to the Claisen condensation, the Dieckmann condensation is driven to completion by deprotonation of the initially formed P-keto ester. Thus, at least one of the ester groups must have two a-hydrogens for the reaction to proceed. 

Undesirable side-reactions, such as Dieckmann ring closure and Claisen condensation reactions, often compete with the acyloin condensation. 

Claisen (cf. Volume 2, Chapter 3.4) and Dieckmann (,cf. Volume 2, Chapter 3.5) condensation reactions work well with thiocarboxylic esters (equations 33 and 34). ... 

Related reactions Dieckmann condensation, Baker-Venkataraman rearrangement ... 

Bunce, R. A., Harris, C. R. Six-membered cyclic (i-keto esters by tandem conjugate addition-Dieckmann condensation reactions. J. Org. Chem. 1992, 57, 6981-6985. 

Toda, F., Suzuki, T., Higa, S. Solvent-free Dieckmann condensation reactions of diethyl adipate and pimelate. J. Chem. Soc., Perkin Trans. 11998, 3521-3522. 

The product this time is a 3-ketoester. A suitable base would be the alkoxide that is derived from the parent alcohol of the ester, because it does not matter if the ester undergoes transesterification that is, where one alkoxy moiety is exchanged for another. Note that, instead of the anionic adduct just picking up a proton, a alkoxide anion is eliminated on the formation of the carbonyl group. If both ester groups are in the same molecule, then an internal condensation reaction is possible. This is called the Dieckmann cyclisation, and works best when the ring formed contains five, six or seven members. 

Dieckmann condensation reactions of diesters normally should be carried out in dried solvent under reflux under an inert atmosphere [21, 22]. Furthermore, Dieckmann reactions are often carried out under high dilution conditions in order to avoid intermolecular reaction [21, 22], However, it was found that the reaction of diethyl adipate (58a) or pimelate (58b) proceeds efficiently in the absence of solvent under air [23]. It is also possible to isolate the reaction products from the reaction mixture directly by distillation [23], These results establish a completely solvent-free procedure throughout the reaction and work-up of the reaction mixture. This is a very clean, green, simple and economical procedure. 

Figure I 1.2 Example of a disconnection or transformation of the structure on the left, affording the synthon on the right. The reverse of this transform (induced by base) is the Dieckmann condensation reaction.

The cyclization reactions described in this chapter and, occasionally, even the acyclic condensation reactions, can often be prefaced by a different type of process such as a Michael reaction. We shall term such a sequence a tandem reaction and a number of these have already been described. Others will be collected here to illustrate the types of processes that have been observed. The cycloenones (198), when treated with a nucleophile (199) under basic conditions, react in a Michael fashion to give the intermediates (200), which then undergo the Dieckmann reaction to give the bicyclic dione (201). Similarly, methyl cinnamate (202) reacts with the nucleophile (203) in the same tandem sequence to give the cyclopentanone (204) as a diastereomeric mixture (Scheme 89). ... 

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