Dieckmann transform

The carbon-carbon bond forming potential inherent m the Claisen and Dieckmann reac tions has been extensively exploited m organic synthesis Subsequent transformations of the p keto ester products permit the synthesis of other functional groups One of these transformations converts p keto esters to ketones it is based on the fact that p keto acids (not esters ) undergo decarboxylation readily (Section 19 17) Indeed p keto acids and their corresponding carboxylate anions as well lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation... 

In its present form, intermediate 12 is not a viable substrate for the crucial Dieckmann condensation it must undergo prior epimerization at C-16. When intermediate 12 is treated with sodium methoxide in hot methanol, enolization at C-16 occurs and an equilibrium is established between 12 and a diastereomeric substance, intermediate 11. Once formed, 11 can either revert back to 12 through the planar enolate form, or it can participate in a productive cyclization reaction to give a new six-membered ring. Under these conditions, the desired transformations take place with exceptional facility to give, after acidification of the reaction medium, enol ester 10. 

Obviously, use of such databases often fails in case of interaction between additives. As an example we mention additive/antistat interaction in PP, as observed by Dieckmann et al. [166], In this case analysis and performance data demonstrate chemical interaction between glycerol esters and acid neutralisers. This phenomenon is pronounced when the additive is a strong base, like synthetic hydrotalcite, or a metal carboxylate. Similar problems may arise after ageing of a polymer. A common request in a technical support analytical laboratory is to analyse the additives in a sample that has prematurely failed in an exposure test, when at best an unexposed control sample is available. Under some circumstances, heat or light exposure may have transformed the additive into other products. Reaction product identification then usually requires a general library of their spectroscopic or mass spectrometric profiles. For example, Bell et al. [167] have focused attention on the degradation of light stabilisers and antioxidants... 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

Even fully substituted aromatic compounds can be prepared utilizing the Mi-chael/Dieckmann strategy. As reported by Covarrubias-Zuniga and coworkers (Scheme 2.32) [67], reaction of the anion of l-allyl-l,3-acetonedicarboxylate (2-138) and the ynal 2-139 afforded the intermediate 2-140 which led to the resorcinol 2-142 with spontaneous aromatization under acidic conditions via 2-141 in an overall yield of 32 %. 2-142 was transformed into mycophenolic acid (2-143) in only a few additional steps [68]. 

Besides the Michael addition-initiated domino reactions presented here, a multitude of other anionic domino reactions exist. Many of these take advantage of an incipient SN-type reaction (for a discussion, see above). In addition to the presented SN/Michael transformations [97, 98, 100], a SN/retro-Dieckmann condensation was described by Rodriguez and coworkers, which can be used for the construction of substituted cycloheptanes as well as octanes [123]. Various twofold SN-type domino... 

The 2,2 -bisindole (1384), required for the synthesis of staurosporinone (293) and the protected aglycon 1381, was prepared by a double Madelung cyclization as reported by Bergman. For the synthesis of the diazolactams 1382 and 1383, the glycine esters 1385 and 1386 were transformed to the lactams 1389 and 1390 by DCC/DMAP-promoted coupling with monoethyl malonate, followed by Dieckmann cyclization. The lactams 1389 and 1390 were heated in wet acetonitrile, and then treated with mesyl azide (MsNs) and triethylamine, to afford the diazolactams 1382 and 1383. This one-pot process involves decarboethoxylation and a diazo transfer reaction (Scheme 5.234). 

The Kojima-Sakai approach, which makes use of trans-cis diester 626, is summarized in Scheme LVII This intermediate was homologated by the Arndt-Eistert method, converted to olefin 627, and oxidatively cleaved to produce ultimately the diester 628. Dieckmann condensation was used to construct the diquinane core which was subsequently transformed to 623 by standard reactions. 

The transformation (190 — 191) exemplifies the use of transition metal reagents the reaction probably involves aminopalladation of the C = C bond (77JOC1329). 2,3-Dihydro-4(l//)isoquinolones are obtained by Dieckmann cyclization of 7V-(o-alkoxycarbonylbenzyl)glycine ester derivatives (192 - 193). 

In another study, Buchanan and McLay (104) found that the equatorial oicy- ri clic ketotosylate 36S gave the seven-membered olefinic ester 367 while the,. axial isomeric tosylate 368 gave the seven-membered olefinic ester 371. Again, the reaction of the equatorial tosylate occurs through the fragmen- tation of intermediate 366. The transformation 368- 371 can be explained by the stereoelectronically controlled retro-Dieckmann fragmentation of 369 followed by the elimination of the tosylate group from 370. 

A library of di- and trisubstituted 5-amino-l 77-1-benzazepine derivatives was assembled through attachment of a preformed 1-benzazepine unit to an aminomethylated polystyrene resin. The initial solution phase synthesis of the 1-benzazepine moiety was based on an intramolecular Dieckmann cyclization (type d) followed by a ketone to primary amino group transformation via reduction ( NaBH3CN) of an imine intermediate <2007JC0487>. 

The latter, with methylacrylate, using Triton B as a catalyst, was transformed into the methylpimelate 189 yielding, on Dieckmann cyclization, the ketoester 190. Upon acid treatment 190 gave the keto nitrile 191. Reduction (LiAlHJ of 191 led, in poor yield, to the hydroxyaldehyde 192. A two carbon unit was added to the aldehydic... 

Methods based on the pyridine to thieno[3,2-c]pyridine transformation are less well developed. Most of the above-described procedures are based on the nucleophilic displacement of the substituent at position 4 of the pyridine ring with a sulfur-containing fragment followed by cyclization of the resulting product. For example, the reaction of 4-chloropyridines 286 with methyl thioglycolate produced 287 and 288 in one step as a result of the replacement of the chlorine atom and Thorpe or Thorpe Dieckmann cyclization (1987JHC85). 

The reaction of tetrachloropyridine 289 with sodium hydrosulfide giving only 4-mercapto derivative 290, which was transformed (1996KGS364) into compound 291 in 77% yield (with respect to mercaptopyridine 290) by 5-alkylation and Dieckmann cyclization, is another example of the application of this approach. 

The diesters (341) participate in a Dieckmann condensation giving heterocycles (25) (60-70% yield) <84JCS(Pl)l50l) and this is a transformation of the general type (294)->(290). 

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