Dieckmann ring closure

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

After an interval of more than 20 years, a second synthesis of ( )-deserpidine and the achievement of some stereoisomers of ( )-raunescine (114) have been reported by Szdntay and co-workers (250,255). The basic idea of this linear total synthesis was similar to that utilized by them for the synthesis of yohimbine alkaloids. First, tetracyclic key intermediate 467 was prepared (253), in which the methoxy substituent of the side chain, on the one hand, represents the future C-18—O bond of the end product and will, on the other hand, control the regioselectivity of the Dieckmann ring closure. 

There are many odier named reactions that follow die same general features but differ as to die type of enolate or the carbon electrophile. These include the Reformatski reaction, the Darzens reaction, and the Dieckmann ring closure. They were in widespread use for many years and were named as a convenient way to characterize the reactants employed and type of product which results. The reason that diere are so many variations on the same theme is that control of the reaction products depends on die ability to generate a particular enolate nucleophile and... 

The pyrrolylthioacetate (105) undergoes Dieckmann ring closure when treated with sodium hydride to give the thieno[2,3-6]pyrrole-2,4-dicarboxylate (106) (65JOC184). 

Undesirable side-reactions, such as Dieckmann ring closure and Claisen condensation reactions, often compete with the acyloin condensation. 

These side reactions can be minimized by adding trimethylsilyl chloride to the reaction mixture as an alkoxide scavenger. This traps the enediolate dianion as a bis-silyl enol ether, and traps the sodium or potassium alkoxides, which are catalysts for the Dieckmann ring closure, as neutral silyl ethers." The resultant bis-siloxy cycloalkenes are either isolated or converted in situ to a-hydroxy ketones by alcoholysis or by acid hydrolysis. ... 

For the synthesis of matrine the penultimate intermediate was 2,6-dioxoquinolizidine (CXLV). The Schilf s base CXLII was reduced and converted to the lactam CXLIV. Dieckmann ring closure, hydrolysis, and decarboxylation gave CXLV which, following a double enamine synthesis with acrylonitrile, and final hydrogenation gave dZ-matrine. Hence the synthesis of dZ-leontine (CXXXVI) (allomatrine) is available. 

III. Claisen condensations, in which -keto carbonyl compounds are formed by the loss of a negative ion from an incipient hemiketal (Claisen condensations, and Dieckmann ring closures). 

A similar mixture in whieh the ( )-isoretronecanol predominated resulted from the Dieckmann ring closure of methyl 3-(2 -carbomethoxy-A-p5T rolidyl)propionate (XLII) to XLIII followed by the cyanhydrin synthesis. 

Dieckmann ring-closure. The mechanism of formation of (63) from (64) and indole has been investigated and the di-indole (65) shown to be an inter-... 

The synthesis and antitumor activity of thieno[2,3-Z ]azepin-4-one based antineoplastic agents was reported [147]. The meaningful structure-activity relationships have been established in monocarbonyl and dicarbonyl series of thieno[2,3-Z)]azepin-4-one 70, 71 (Figme 4) prepared by Dieckmann ring closure reaction in multistep reaction fi-om substituted 2-aminothiophenes. 

Cz. Szantay, L. Toke and K. Honty, Tetrahedron Lett., 1665 (1965) Chem. Ber., 102, 3248 (1969). Subsequently these authors reported improvements in the Dieckmann ring closure of ring E in the late stages of this synthesis, Cz. Szantay, K. Honty, L. Toke, A. Buzas and J. P. Jacquet, Tetrahedron Lett., 4871 (1971). 

This modification has become the standard procedure for the acyloin ester condensation. By doing so, the formation of products from the otherwise competitive Dieckmann condensation (Claisen ester condensation) can be avoided. A product formed by ring closure through a Dieckmann condensation consists of a ring that is smaller by one carbon atom than the corresponding cyclic acyloin. 

This synthetic route is based on ring closure by Dieckmann condensation of 1,2-bis-carbalkoxyalkylpyrrolidines. It has gained special importance during the last few years, after application to several total syntheses of naturally occurring pyrrol izidine bases. The usual starting compounds employed in this route are esters of a-pyrrolidineacetic acid, proline, and their homologues, which are converted into N-substituted dialkyl dicarboxylates. The esters of the dicarboxylic acids are subjected to Dieckmann condensation and subsequent ketonic hydrolysis the resultant ketones are used in further reactions. 

Ring closure of certain thiophene diesters 74a or cyanoesters 74b under Dieckmann conditions (EtOH/EtONa) has recently been shown to give thieno[2,3-6]pyrroles (75a, b) in high yield (65-90%).72 A thieno-[2,3-6]pyrrole diester (75 R5 = OCH2COzEt) prepared in this way failed to undergo further cyclization to the tricyclic system 76 under the same conditions.7215... 

Tetrahydro-l-benzazepin-2-ones are formed from a-tetralone by Beckmann or related reactions (CHEC 5.16.4.1.1). Classical ring closures (of the Friedel-Crafts, Dieckmann, etc. types) can also be applied to benzazepine synthesis (74AHC(17)45). 

The rules of Baldwin (55) for ring closure in trigonal systems (see p. 171 for an introduction) are the following 3- to 7-Exo-Trig processes (152-156) are all favored processes. 3- to 5-Endo-Trig (157-159) are disfavored but 6- and 7-Endo-Triq (160-161) are favored. The literature is replete with examples of 3- to 7-Exo-Trig for instance, lactonization of u-hydroxy-acids and esters are of this type, the formation of lactams from w-aminoacids and also the Dieckmann cyclization of diesters. 

Classical ring closures (of the FriedelCrafts, Dieckmann, etc., types) can be applied to benzazepine synthesis <1974AHC(17)45>. Particularly useful are approaches to benzazepines based on transition metal-catalyzed cyclizations , as illustrated by the synthesis of 1-benzazepine derivative 149 in high yield by Ru-catalyzed ring-closing metathesis with Grubbs I catalyst (Scheme 87) <2005JOC1545>. 

The classical Dieckmann reaction occurs under equilibrium conditions, the initial step involving the base-catalyzed formation of the ester enolate anion. The rate-determining step is ring closure, the subsequent loss of the alkoxide being rapid (Scheme 14). ... 

Seven-membered and larger rings can be prepared by this method and the yields can often be satisfactory. Carefully controlled nonequilibrium conditions and high dilution techniques are often required. Medium rings (9-12) are either not formed, or formed in low yield, a combination of a Claisen condensation followed by a Dieckmann reaction giving macrocyclic diketones. The conformational energies of the linear precursor influences ring closure. Examples are illustrated in Scheme 19. 

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