Dieckmann-type condensation

Triflates of titanium and tin are effective catalysts for various condensations of carbonyl compounds [I2I, 122, 123, 124, 125] Claisen and Dieckmann type condensations between ester functions proceed under mild conditions in the presence of dichlorobis(trifluoromethanesulfonyloxy)titaiiiuin(rV) and a tertiary amine (equations 59 and 60) These highly regio- and stereoselective condensations were used successfully m the synthesis of carbohydrates [122]... 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

Scheme 3 Examples of Dieckmann-type condensation (a) and [2 + 2 + 2] cycloaddition (b) leading to functionalized and ring-fused 2-pyridones...

The novel phosphonium salt (372) has been used in a non-stereoselective synthesis of members of the pulvinone group (373). This brief and useful method, which produces (E)-pulvinones for the first time, is complemented by an alternative approach to these compounds using a Dieckmann-type condensation of diester (374) to establish the tetronic acid... 

Mono-thiol ester version of the Dieckmann-type condensation ... 

The preparation of succinic esters by anion coupling with polyhalides has been described/ The scope of the Wurtz coupling of a-halogenoesters to give alkyl-substituted succinic esters has been investigated optimum conditions utilize a-bromoesters and zinc in THF, the presence of copper(n) salts being mandatory to avoid Dieckmann-type condensation to form p-ketoesters. 

There are exacdy 10 different two-bond disconnections possible for the construction of 3-pyrroUn-2-ones. Eight of these intermolecular approaches have appeared in the Uterature and are depicted below (Scheme 54). For example, a type ac cyclization could combine a Dieckmann-type condensation (to form bond c ) and a lactamization (to form bond a ). The most commonly utilized intermolecular approaches to 3-pyrrolin-2-ones involve type ae cyclizations followed closely by type ab (carbon-ylations) and type ac cyclizations. Only a small handful of reports of the other types of intermolecular approaches have been reported. 

Thiepane (35) has been synthesized by an intramolecular radical addition of the thiyl radical (equation 59) which was generated by photolysis of a thiol (71TL2025). Similarly, C—S bond formation has been achieved (equation 60) by an intramolecular condensation of 6-mercaptohexanoic acid to give the thiolactone, thiepan-2-one (135) (64MI51700). A Dieckmann-type base-catalyzed cyclization of a diester precursor followed by acid-catalyzed hydrolysis and decarboxylation has been used in the synthesis of thiepan-3-one (41) as indicated in equation (61) (52JA917). 

The initial step is a Claisen condensation involving both the a-methyl and a -methylene groups, followed by a Dieckmann-type cyclisation to form ethyl 4-methyl-2,3,5-trioxocyclopentylglyoxalate (35). When heated with hot aqueous... 

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. 

CLAISEN - GEUTER - DIECKMANN Ester condensation Synthesis o( open chain or cyclic p keloesters by aldol type condensation... 

Pyrido[2,3-(7]pyrimidincs 23, unsubstituted in the 2,4-positions, have been synthesized by condensation of ethyl 4-aminopyrimidine-5-carboxylate with several esters, phenylacetonitrile, phenylacetamide, or malonic ester chloride.173 In the first step, the 4-amino group reacts with the ester, nitrile, or acid chloride function of the cyclization partner, ring closure then being effected by a Dieckmann-type cyclization. 

The Dieckmann intramolecular condensation of diesters, which is used for the formation of rings B, C, and, particularly, D, has found incomparably wider use. In this reaction, cyclic )3-keto esters are first formed in the synthesis of ring C (93) —(94) they are immediately methylated further (Scheme 8), and in the synthesis of ring D (95) — (98) cyclization to compound (96) is followed by saponification and decarboxylation (Scheme 82). Instead of cyclization of diesters of type (95) in the presence of alk-... 

More recently, Wang and co-workers reported on a solid-phase total synthesis of 1-p-methylcarbapenem 97 because of interest in its potent broad-spectrum antibiotic activity. In this total synthesis (Scheme 3.19), azetidinone 92, bearing a chiral auxiliary, was loaded onto polystyrene-diethyl-silane resin 91 to give 93, which was condensed with allyl bromoacetate to give supported azetidinone 94. Treatment with TMSCl in the presence of NaN(TMS)2 and diphenyl phosphorochloridate (DPPC) promoted a Dieckmann-type cyclization to give supported vinyl phosphate 95 with concomitant release of the chiral auxiliary. Vinyl phosphate resin 95 was treated with thiophenol to give supported 1-P-methylcarbapenem 96, which was released from the solid support upon treatment with tetra-H-butylammonium fluoride (TBAF). 

Dieckmann-type reaction mechanism and not through a Stobbe-type reaction mechanism, as is the case in the Hinsberg reaction with oc-diketones. The usefulness of the Gewald reaction for the synthesis of 2-amino-3-carbonyl-substituted thiophens, important building-blocks for the synthesis of fused thiophens, has clearly been demonstrated. From the condensation products of cycloalkanones and nitriles (1), the thiophens (2) were obtained through the reaction with sulphur in the presence of diethylamine. Similarly, from the dithiacyclo-octane derivative (3), the thiophen (4) was prepared. In connection with the synthesis of psychophar-maca of the diazepine type, several substituted 2-amino-3-benzoylthiophens (5) were prepared through the reaction of phenacyl cyanides with aldehydes... 

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. 

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... 

Dieckmann condensation of the diester 523 gives compound 524 which is readily oxidized to the pyridazinium-5-olate 525 (R = COjEt). This betaine (525 R = COjEt) has been converted into a number of derivatives (525 R = H, CO2H, Br, NHPh, SCH2Ph). Photolysis of the betaines 525 (R = H, CO2Et) results in rearrangement to isomeric 4(3//)-pyrimi-dinones. Full details of another study of this type of photochemical rearrangement of pyridazinium-5-olates (142) have now been published. ... 

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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