Dieckmann condensation of diesters

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>. 

Secondly, Dieckmann condensation of diester 211 with sodium hydride in benzene, followed by hydrolysis and decarboxylation. 

Tetracyclic keto ester 467, prepared earlier (253), was treated with the anion of diethyl methoxycarbonylmethylphosphonate in dimethylformamide. The reaction supplied the unsaturated ester 492, which was catalytically hydrogenated to diester 493. Dieckmann condensation of 493 yielded two nonenolizable keto esters (494 and 495), which could be separated by fractional crystallization. Sodium borohydride reduction of 18a-methoxyyohimbinone (494) gave two alcohols (496 and 497) in a ratio of about 10 1 at the same time, reduction of 180-methoxyyohimbinone (495) furnished another two stereoisomeric alcohols (498 and 499) in approximately equal amounts. Demethylation of the four stereoisomers (496-499) resulted in the corresponding 18-hydroxyyohimbines (500-503)... 

Cyclization of diallylic halides 0-90 Cyclization of 1,3-diols 0-94 Internal malonic ester synthesis 0-102 Carbonylation of 1,4-dihalides 0-108 Internal condensation of diesters (Dieckmann)... 

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. ... 

Dieckmann condensation of appropriately substituted diesters or cyanoesters has been reported to give good yields of some thieno[2,3-6]pyrrole derivatives. For example, thiophene diester (186) afforded the thieno[2,3- ]pyrrole derivative (187) in good yield upon... 

The complex WOCI4—Cp2TiMe2 was used for the metathesis of ethyl oleate (51) to give diethyl 9-octadecenedioate (52). Civetone (53) was synthesized by the Dieckmann condensation of this diester, followed by decarboxylation [20], Homometathesis of terminal alkenes is useful, because it yields symmetric internal alkenes and ethylene, which can be removed easily. Metathesis of 10-undecenoate (54) proceeds smoothly to give the diester 55 [20],... 

Reaction of 17/J-acetoxy-la,2oc-epoxy-lj3-methyl-5a-androstan-3-one (224) with acid gave an isomeric mixture of A-nor-2-oxo-steroids (225) carrying a formyl group at C(l). Treatment of this mixture with base provided exclusively the l/ -methyl-A-nor-steroid (226).The 3a-methyl-A-norandrostane derivative (230) has been prepared as shown in Scheme 16, i.e. by oxidative cleavage of ring A of the 3-keto-derivative (227) followed by Dieckmann condensation of the diester (228), and methylation and decarboxylation of (229). - ... 

The Dieckmann condensation is usually defined to include only intramolecular condensations of diesters. ... 

The synthesis of (32) and other analogues, described below, was carried out as shown in Scheme 4.1 by treating 2-nitroaniline with acrylonitrile followed by catalytic hydrogenation to a phenylenediamine. From this, the PBI nucleus was formed with carbethoxyacetimidate hydrochloride, followed by Dieckmann condensation of the resulting diester. Condensation of the ester with an appropriate amine afforded the target PBIs. 

The anion from (70.5) attacks the nitrile group and a 4-aminopyridine ring is formed in this example, the product is related to the antibacterial agent nalidixic acid. 5-Phenyl esters are useful in regioselectively directing a Dieckmann condensation of the diesters (70.6) to carbacephems. Dieckmann reactions usually requite heating but the enaminic ester (70.7) undergoes cyclization without external heat. 

The crown ethers (61) have been synthesized by a novel Dieckmann condensation of the diester (62) under high dilution. The ester and ketone groups are readily removed. 

A six-membered ring j8-keto ester is formed from a Dieckmann condensation of a 1,7-diester. 

Mannich base XL provided the tetracyclic ketoester XLI. Construction of ring E was then initiated by reacting compound XLI with the phos-phonic acid derivatives (XLIIa) or (XLIIb) to yield the unsaturated diester XLIIIa or the nitrile XLIIIb which were subsequently hydrogenated to XLIVa and XLIVb, respectively. Dieckmann condensation of XLIVa in homogeneous phase (NaH in dimethyl sulfoxide) effected its cyclization to the pentacyclic derivative XLV which was mostly in the enolic form. Structural and stereochemical proof of XLV was provided by its hydrolysis and decarboxylation to ( )-yohimbone (XLVI), further converted to (+ )-yohimbane (XLVII) by Wolff-Kishner... 

Crowley and Rapoport f described the Dieckmann condensation of solid-supported radiolabeled mixed diesters 36 (Scheme 1.6.18) which afforded two P-ketoesters, one being released into solution and the other staying grafted onto the polymer. 

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... 

Another route was needed for the preparation of alkyl and alkoxy substituted analogs in die pyrrolo[2,3- ]pyiidine series. An attractive route was utilization of the highly function ized hetero[23- lpyndine intermediate available fiom the Dieckmann condensation of a diester intermediate0. The p> dine tetraesters 12 required by diis route were readily prepared in three steps. Mchael addition of 8 to 9 followed by intramolecular ring closure afforded pyridine 10, which was converted to the 6-chloropyridine 11 by phosphorous oxychloride. Treatment of the 6-chloropyridine triester 11 with sarcosine and sarcosine esters at room temperature afforded a series of 6-aminopyridines 12a-c. 

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-... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

The intramolecular version of ester condensation is called the Dieckmann condensation.217 It is an important method for the formation of five- and six-membered rings and has occasionally been used for formation of larger rings. As ester condensation is reversible, product structure is governed by thermodynamic control, and in situations where more than one product can be formed, the product is derived from the most stable enolate. An example of this effect is the cyclization of the diester 25.218 Only 27 is formed, because 26 cannot be converted to a stable enolate. If 26, synthesized by another method, is subjected to the conditions of the cyclization, it is isomerized to 27 by the reversible condensation mechanism. 

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. 

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). 

Interestingly, the dienolate generated from di-/er/-butyl adipate underwent oxidative cycliza-tion with copper(II) chloride to afford di-/m-butyl cyclobutane-l,2-dicarboxylate (12) in 21 % yield, together with the competitive Dieckmann product (30%) as well as unreacted starting material (17%).20 The formation of the cyclobutane diester is presumably due to the steric hindrance of the /e/v-butyl groups, which impedes the Dieckmann condensation and thus favors, to some extent, an oxidative coupling reaction.20... 

Similar in style to the above are the base-catalyzed intramolecular cyclizations of diesters (116) and substituted salicylaldehydes (117), Dieckmann and Perkin condensations, respectively (36JCS212, 36JCS419, 40JCS787). 

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