3-Keto esters Dieckmann cyclization

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones (Section 23.6). Called the Dieckmann cyclization, the reaction works best on 1.6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a five-membered cyclic /3-keto ester, and cyclization of a 1,7-diester gives a six-membered cyclic /3-keto ester. 

These intramolecular homoconjugate additions provide a simple entry into fura-noid systems. The p-keto-ester (461) cyclizes in a spiro mode to (462a), whereas with dimsylsodium the isomer (462b) is formed. Similarly, the keto-ester (463 R = COjMe) is cyclized to (464) by sodium hydride, but the ketone (463 R = H) affords only the Dieckmann product (465) under these conditions. ... 

Detailed mechanisms of Dieckmann cyclizations on PS have been elucidated by isotopic labeling experiments/ In many cases scrambling of " C-carbonyl carbon atoms by reversible condensations accompanies formation of the desired products, as shown in equation (32). Yields of six-membered j -keto esters from cyclization of PS-bound unsymmetrical diesters have been good, but attempts at PS-bound synthesis of the nine-membered jS-keto ester failed, as have attempts to perform that cyclization in solution. Small amounts of cyclodimers were formed as shown in equation (33). 

Dieckmann cyclization (Section 21 2) An intra molecular analog of the Claisen condensation Cy die p keto esters in which the ring is five to seven membered may be formed by using this reaction... 

The mechanism of the Dieckmann cyclization, shown in Figure 23.6, is the same as that of the Claisen condensation. 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 /3-keto ester product results. 

The cyclic /3-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). For example, alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate yields a 2-alkylcvclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) /3-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclohexanones and cyclopentanones. 

Mechanism of the Dieckmann cyclization of a 1,7-diester to yield a cyclic /3-keto ester product. 

Dieckmann cyclization of diethyl 3-methylheptanedioate gives a mixture of two /3-keto ester products. What are their structures, and why is a mixture formed ... 

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

Dieckmann Condensation The intramolecular equivalent of a Claisen condensation where dicarboxylic acid ester undergoes base-catalyzed cyclization to form a P-keto ester. 

After oxidation of the vinyl group, the C ring is constructed by a Dieckmann cyclization. The resulting jS-keto ester is subjected to nucleophilic decarboxylation by phenylthiolate [step F (4-6)]. 

Intramolecular Dieckmann cyclization of polystyrene-bound pimelates has been used to prepare (l-keto esters (Entry 4, Table 3.41). Oxidative cleavage reactions leading to the formation of aldehydes include the ozonolysis of resin-bound alkenes, the periodate-mediated cleavage of 1,2-diols, and the oxidation of Wang resin derived ethers (Entries 5-7, Table 3.41). 

The desired ketone, cyclopentanone, is derived from the corresponding j8-keto ester. This key intermediate is obtained from a Dieckmann cyclization of the starting material, diethyl hexanedioate. 

Examine each carbon that is a to an ester function to see if it can lead to a five-, six-, or seven-membered cyclic /3-keto ester by a Dieckmann cyclization. 

Conversion of this intermediate to the desired /V-m c(liy 1 -4-pi pcridonc requires a Dieckmann cyclization followed by decarboxylation of the resulting /3-keto ester. 

Various convergent Pb(iv)-promoted coupling reactions between vinylstannanes and cyclic /3-keto esters were used to prepare tetrasubstituted a-alkyl-/3-ketoesters which underwent subsequently a tandem alkylation, anion-accelerated oxyCope rearrangement and a trans-annular Dieckmann cyclization to afford bridgehead enone-containing... 

In the absence of the MeaSiCI, the main product from this reaction becomes the cyclic keto-ester below, which arises from base-catalysed Dieckmann cyclization (see Chapter 28) of the diester. 

The Dieckmann cyclization is used to form cyclic P-keto esters. 

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. 

Dieckmann cyclization of diethyl adipate can be described by the two successive equilibria shown below. Use SpartanView to obtain the energies of diethyl adipate, the keto ester, the keto ester enolate ion, ethanol, and ethoxide anion, and calculate AH° for both steps. Which step is more favorable ... 

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