Intramolecular Claisen-type condensation

The mechanism of the Madelung indole synthesis has not been fully established. An intramolecular Claisen type condensation is presumably involved in the process. ... 

From the previous discussion, it is evident that intramolecular aldol condensations are commonplace in this field. However, intramolecular Claisen-type condensations can be accomplished by the use of magnesium methoxide, as in the formation of phoroglucinol derivative 328 (70CRV553). The common intermediate 323 (undetermined ionization state) accounts for both formation of 324 through an aldol condensation (C3—C—C/C6) and formation of 328 by Claisen condensation (C3—C—C—C/C5). Further examples of directed cyclizations, depending on the base used, are gathered in the review by Money (70CRV553). 

Scheme 9.146. A representation of an intramolecular Claisen-type condensation (an acyloin condensation) in which the diethyl ester of 1,6-hexanedicarboxylic acid (diethyl adipate, CH3CH202C(CH2)4C02CH2CH3)) undergoes cychzation to yield ethyl 2-oxocyclopentanecarboxylate in the presence of ethoxide anion ( OCH2CH3) in ethanol (ethyl alcohol, CH3CH2OH) solvent.

HO Me Claisen-type condensation Intramolecular Heck reaction... 

The first cyclative cleavage of a small molecule was Crowley and Rapo-port s study41 of intramolecular Dieckmann condensations on solid phase (Fig. 13), which was complicated by the reversible nature of the cyclization. Despite the unique opportunities afforded by C-C rather than C-X bond formation during cleavage, there are few examples from the combinatorial age. A modern version of the Claisen-type condensation by Kulkarni and Ganesan42 uses a strongly acidic active methylene group to ensure unidirectional cyclization, and furnishes tetramic acids with three points of diversity. 

Auxiliary cleavage with concomitant carbon-carbon bond formation is a particularly attractive option, which has been demonstrated in a bimolecular sense using the dianion of methyl sulfone (giving a methyl ketone), and in an intramolecular sense using a Claisen-type condensation of a p-acetoxy enolate (giving a 5-lactone). An interesting halolactonization procedure has... 

It is not unreasonable to expect that a Claisen-type condensation might also occur intramolecularly. That is, both the anion a- to a carbonyl group and another carbonyl group might be present in the same molecule. As shown in item 6 of Table 9.9 and Scheme 9.146, when the diethyl ester of 1,5-hexanedicarboxylate (diethyl adipate CH3CH202C(CH2)4C02CH2CH3), is treated with ethoxide (-OCH2CH3)... 

In 2001, Hinterding and coworkers reported on a Claisen condensation/reduction sequence. They used an intramolecular Claisen-type reaction to cleave off the Evans... 

The situation is even more complex during polymerization, because a 1,2-addition can take place onto the ester groups of both the monomer and the monomeric units in the chains. This type of reaction can be either an intramolecular Claisen condensation, thus a backbiting reaction, with formation of cyclics (equation 19) or an intermolecular reaction... 

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). 

CHS (Fig. 2), the most studied member of the type III PKS family, is a ubiquitous enzyme in plants that catalyzes the first committed step in flavonoid biosynthesis, the elongation of the starter molecule 4-coumaroyl-CoA by addition of three acetate units derived from three molecules ofmalonyl-CoA [19]. After binding ofthe 4-coumaroyl moiety to the active site Cysl64, sequential polyketide chain elongation is initiated by the decarboxylation of malonyl-CoA to form an acetyl-CoA carbanion, followed by an intramolecular Claisen condensation step and subsequent cyclization and aromatization, yielding chalcone [20]. 

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