Dieckmann cyclization addition

Claisen rearrangement, 660 conjugate carbonyl addition reaction, 725-726 Curtius rearrangement, 935 cyanohydrin formation, 707 dichlorocarbene formation, 227 Dieckmann cyclization reaction, 892-893... 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

The ketone (48) can be obtained by Dieckmann cyclization, but this reaction failed for other isomers of (48) (72JCS(Pl)885). Friedel-Crafts cyclization has been used to obtain the N-tosyl ketone (49) (72JCS(Pl)2l3). Ring expansion reactions based on dibromocarbene additions have also been used to prepare benzo derivatives (72JCS(Pl)889). 

Acetaminothiophene has been prepared by a Hofmann rearrangement of thiophene-3-carboxamide (equation 49), or by a Beckmann rearrangement of the 3-acetylthiophene oxime (Section 3.14.3.4). Dimethyl 4-amino-2,3-thiophenedicarboxylate was formed in excellent yield from the oxime of the 4-ketotetrahydrothiophene diester, which is readily available by addition of thioglycolate to dimethyl fumarate, followed by a Dieckmann cyclization (equation 50 Section 3.15.2.2.2). 

Michael addition of methyl 3-mercaptopropanoate to methyl 3-methylbut-2-enoate and Dieckmann cyclization of the resulting diester yields 2,2-dimethyltetrahydrothiopyran-4-one 539 (Scheme 220) <2005HCA1922>. Similarly, diethyl thiodipropanoate, accessible from ethyl propenoate by treatment with NaSH in methanol, cyclizes to ethyl 4-oxotetrahydrothiopyran-3-carboxylate under basic conditions. The carbon skeleton has also been provided by 1,4-pentadienones <1995JOC1665> and H2S in ethanol has been used as an alternative source of the heteroatom (Scheme 221) <1999SL735>. 

Conjugate addUion-cyclization. 3-Substituied 2-carbomethoxycyclopentanones are prepared conveniently in one step from dimethyl (2E)-hexenedioate by conjugate addition of lithium dialkyl cuprates or higher-order cyan[Pg.348]

N,N-disubstituted benzylamine (65) was allowed to react in a high-dilution Dieckmann cyclization to give the ketoester (66) (88%), which displayed a typical transannular interaction [Eq. (23)]. Conversion into the perchlorate salt produced a bicyclic structure (67). Hydrogenation of 67 gave the de-benzylated salt (68) in 69% yield. The stereospecificity of this reaction probably arises from cis-addition of the hydrogen atoms from the less hindered side of the likely intermediate iminium salt (69). The free base derived from 68 was reduced to give ( )-isoretronecanol (22) (53%) with an isomeric purity of 98%, as determined by GLC analysis. 

Bixchler Napiralski, Dieckmann cyclization [15], Suzuki reaction [48], Wittig reaction, ozonolysis, condensation, esterification, nucleophilic substitution [49], Henry reaction, 1.3-dipolar cyclo-addition, electrophilic addition [50], oxidation chloride -> aldehyde [50], sulfide —> sulfone [51], alcohol —> ketone, Arbuzov reaction (phosphine-phosphorox-ide) [52], reduction hydration [45], ester -> alcohol [49, 53]... 

In the conventional method of carrying out the Dieckmann cyclization of diethyl adipate to produce 2-carboethoxycyclopentanone311> a mixture of sodium and toluene is heated in an oil bath and agitated with a sturdy stirrer during slow addition of the ester at 60-110° (8 hrs.). Chemists310 of Dr. Th. Schuchardt Co., Munich, found that the process is simplified and improved by replacing the toluene by DMSO. The reaction then proceeds in homogeneous solution and requires no special stirrer. 

The addition of salts of /0-keto-esters to (67) at room temperature gave (68). A route to modified benzomorphans is provided by Dieckmann cyclization of (69) after hydrolysis, this affords (70). 

N,N-Dichlorurethan as pseudohalogen 24, 563 N,N-Dichlorurethans, addition to 1,3-dienes 24, 554 NjN -(Dicyan)amidines 24, 360 Dicyclohexylcarbodiimide as reagent 24,181 Di(cyclopentadienyl)metal compounds s. Metallocenes Dieckmann cyclization (s. a. under Michael addition)... 

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