Dieckmann cyclisation

Crossed Claisen reactions with two different esters, each of which has a-H atoms, are seldom useful synthetically as there are, of course, four possible products. Crossed Claisen reactions are, however, often useful when one of the two esters has no a-H atoms, e.g. HCOzEt, ArC02Et, (C02Et)2, etc., as this can act only as a carbanion acceptor. Such species are in fact good acceptors, and the side reaction of the self-condensation of the other, e.g. RCH2C02Et, ester is not normally a problem. Intramolecular Claisen reactions, where both C02Et groups are part of the same molecule [e.g. (123)], are referred to as Dieckmann cyclisations. These work best, under simple conditions, for the formation of the anions of 5-, 6- or 7-membered cyclic / -ketoesters... 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

A Failed Thorpe-Dieckmann Cyclisation "Obvious" Reactions are not Always Well Behaved. 

The forward synthetic reaction (formulated in Expt 7.9) is thus an initial mixed Claisen ester condensation, followed by a Dieckmann cyclisation, hydrolysis and decarboxylation. Indane-l,3-dione is used for the synthesis of the trione, ninhydrin (Expt 5.99). 

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. 

A new, stereospecific synthesis of (+)-isoretronecanol, by a transannular route, has been developed by Leonard et al. Dieckmann cyclisation of NN-bis-(y-ethoxycarbonylpropyl)benzylamine gave ethyl l-benzyl-5-oxo-l-azacyclo-octane-4-carboxylate (20), whose perchlorate was shown to possess a bicyclic structure. Hydrogenation of this perchlorate in ethanol, using palladised charcoal catalyst, afforded ethyl ( )-isoretronecanolate perchlorate (22) as sole product, presumably by stereospecific addition of hydrogen at the less hindered face of the intermediate debenzylated immonium ion (21). Reduction of the free base corresponding to (22), by means of lithium aluminium hydride, gave (+ )-isoretronecanol (23), the stereochemical purity of which was shown by g.l.c. analysis to be >98%. 

The second synthesis of septicine used as starting material ethyl homovera-trate, which was formylated to the a-hydroxymethylene derivative (24). Controlled reduction of (24) with sodium borohydride gave mainly the desired )5-hydroxyester, which was converted into the chloride and condensed with ethyl 2-pyrrolidinyl acetate to yield the diester (25). Dieckmann cyclisation of... 

Olefin metathesis has been used by a number of workers to produce macrocyclic musks. One of the earliest examples is Mol s synthesis of civetone from methyl oleate. This takes advantage of the ideally placed double bond in the starting oleic acid. Unfortunately, the ds-geometry of the olefin is lost on metathesis and a mixture of isomers results. Furthermore, almost half of the weight of the starting material is lost as the unwanted 9-octadecene. Dieckmann cyclisation of the metathetical diester, followed by hydrolysis and decarboxylation, gives a mixture of E- and Z-civetone. The synthesis is shown in Figure 4.59. 

The first synthesis of a jasmonoid, namely dihydrojasmone, took place nine years before the structure of jasmone itself was established. This goal was achieved in 1924 by Hermann Staudinger and Leopold Ru icika in the course of their work on pyrethroids. [84] They carried out a Reformatzky reaction between ethyl laevulinate and ethyl 2-bromoheptanoate, and obtained the desired product, although in poor yield, by a Dieckmann cyclisation, followed by hydrolysis and decarbethoxylation (see next page). 

Relatively little is known about the biosynthesis of civetone and muscone. Ruiicka had recognised already the structural relationship of civetone and oleic acid, and so it could be imagined that civetone might be derived from oleic acid by terminal oxidation and Dieckmann cyclisation. 

Poncet J, Jouin P, Castro B (1990) Tetramic Acid Chemistry Parti. Reinvestigation of Racemisation during the Synthesis of Tetramic Acids via Dieckmann Cyclisation. J Chem Soc Perkin Trans 1 611... 

Further details have appeared concerning the synthesis of 6,9-methano-PGl2 (255) by way of a Dieckmann cyclisation in the key step (ref lb, p 150). The Corey lactone (2h) was converted into the... 

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