Dieckmann condensation, also

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

In a more recent publication the same research group described a Cu(OTF)2/(POEt)3-catalyzed two-component Michael/aldol protocol of 2-112 and ZnEt2 leading to annulated cyclopentanols [46]. They showed that the enolate formed in the 1,4-addition can be trapped not only by a keto moiety, but also by an ester (Dieckmann condensation) or a nitrile functionality present in the molecule. Thus, as depicted in Scheme 2.26, there is a broad product variety. Starting from 2-112, compounds of type 2-114, 2-115 and 2-116 can be obtained via the enolate 2-113. 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Anionic resin capture of solution-phase library products has also been reported. The anion exchange resin A-26 hydroxide 6 was used in a dual capacity to mediate Dieckmann condensations of solution-phase library intermediates and also to affect resin capture of the formed tetramic acids as polymer-bound intermediates (Scheme 7).79 Rinsing, followed by tri-... 

Bicyclic keto esters can easily be prepared by a process called a,a -annulation.29 Thus, treatment of the enamine of cyclopentanone (64) with ethyl a-(bromomethyl)acrylate (98) affords, after work-up, the bicyclic keto ester (99) in 80% yield (equation IS).2911 The mechanism probably involves an initial Michael addition and elimination (or a simple Sn2 or Sn2 alkylation) followed by an intramolecular Michael addition of the less-substituted enamine on the acrylate unit. The use of the enamine of 4,4-bis(ethoxycarbonyl)cyclohexanone (100 equation 26) with (98) gives a 45% yield of the adaman-tanedione diester (101) (yield based on 100 70% when based on 98) via a,a -annulation followed by Dieckmann condensation.29 Enamines of heterocyclic ketones can also serve as the initial nucleophiles, e.g. (102) and (103) give (105) via (104), formed in situ, in 70% yield (Scheme 11 ).29>... 

Bridged systems can also be prepared in high yield by this process.84 For example, treatment of the keto diester (348 Scheme 43) with (61) in basic DMSO gave a 41% yield of the diketo diester (352) by way of the intermediates (349) to (351), involving two Michael additions and final Dieckmann condensation.84 Similar processes have also been used to make other bicyclo[3.3.1]nonanes and related com-... 

Dieckmann condensation under basic conditions yields 3-piperidones (Equation 81) <2004JME5620>. Substituted 4-piperidones are also reported in a Ti(iv)-mediated Dieckmann condensation of diesters (Equation 82) <1995SC177>. The electroreduction of the alkenyl bromide 36 under [Ni(cyclam)](ClC>4)2-catalyzed conditions leads to the piperidone in moderate yields (Equation 83) <1996JOC677>. 

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. 

Due to the availability of long-chained aliphatic dicarboxylic acids by biotechnological processes [124b], a Dieckmann condensation reaction may also possibly be a useful route to produce this macrocyclic ketone [124c]. 

The first total synthesis of estrone itself by Anner and Miescher in 1948 also ended with the construction of the hve-membered ring D. This synthesis differs from that above mainly by the replacement of the naphthalene moiety by a tetralin. Dieckmann condensation of the ester 12-1 gives the hydrophenanthrone 12-2 (Scheme 3.12). Treatment of the... 

The Dieckmann condensation has been employed with success, for total synthesis of some alkaloids, e.g.9 that of tropinone by Willstatter and Bommer,766 and also by various authors767 for synthesis of large-ring ketones. 

Several ester disconnections are covered in this chapter. The Claisen condensation gives a keto-ester and the Claisen disconnection is shown. The cyclic version of this reaction is the Dieckmann condensation, and the Dieckmann disconnection is also shown. 

Tetronic acids (4-hydroxy-2(5//)-furanones) are also an example of 5-membered rings, and they are compounds of potential activity as antibiotics, antiviral and neoplastic agents. The base-promoted Dieckmann condensation is one of the desired methods to produce 3-acyl-tetronic acids. An example is the intramolecular tetrabutylammonium fluoride-promoted Dieckmann cyclization of 53 to give tetronasin (54) in 72% yield. 

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