Dieckmann condensation intramolecular

Dihydrofuranones can be generated by Michael addition of anions derived from a-hydroxyesters to a,/3-unsaturated substrates. The resulting intramolecular Dieckmann condensation yields substituted furanone rings (Scheme 82) (57HCA1157). 

Quinuclidine ring formation starting from piperidine derivatives is carried out usually by (a) intramolecular alkylation or acylation or (b) intramolecular Dieckmann condensation. 

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. 

Original Synthesis. The first attempted synthesis of 5 -biotin in 1945 afforded racemic biotin (Fig. 1). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmann condensation, during which stereochemical integrity was lost, was foUowed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

Application of intramolecular Dieckmann-condensation for the solid-phase synthesis of lactones by Rapoport et al. (7. Macromol. Sci. Chem. 1973,1117)... 

In the first and asymmetric total synthesis of rubriflordilactone A shown below, the advanced intermediate furofuranone was constructed through an intramolecular Dieckmann condensation followed by a cationic deoxygenation reaction (14JA16477). 

In Summary Claisen condensations are endothermic and therefore would not take place without a stoichiometric amount of base strong enough to deprotonate the resulting 3-ketoester. Mixed Claisen condensations between two esters are nonselective, unless they are intramolecular (Dieckmann condensation) or one of the components is devoid of a-hydrogens. Ketones also participate in selective mixed Claisen reactions because they are more acidic than esters. 

Claisen condensation 2 Esters — j8-ketoester 1,7-diester cyclic /3-ketoester (intramolecular Dieckmann condensation) (23-1)... 

We begin with the discussion of intramolecular reactions. An example of a regioselec-tive Dieckmann condensation (J.P. Schaefer, 1967) used an educt with two ester groups, of which only one could form an enolate. Regioselectivity was dictated by the structure of the educt. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Carboxylic esters 1 that have an a-hydrogen can undergo a condensation reaction upon treatment with a strong base to yield a /3-keto ester 2. This reaction is called the Claisen ester condensation or acetoacetic ester condensation, the corresponding intramolecular reaction is called the Dieckmann condensation ... 

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 ... 

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones (Section 23.6). Called the Dieckmann cyclization, the reaction works best on 1.6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a five-membered cyclic /3-keto ester, and cyclization of a 1,7-diester gives a six-membered cyclic /3-keto ester. 

Intramolecular Claisen condensation (Dieckmann cyclization Section 23.91... 

Dieckmann cyclization reaction (Section 23.9) An intramolecular Claisen condensation reaction to give a cyclic /3-keto ester. 

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]. 

This case study deals with an industrial Dieckmann condensation (intramolecular ester condensation Scheme 5.6) considering the laboratory and the operation scale. 

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 reaction starts with the formation of a mixed anhydride and an acetate on treatment with an excess of acetic anhydride at 80 °C. There follows a Dieckmann condensation to give 2-590 and an intramolecular rearrangement/Michael addi-hon/retro Michael addition to afford the desired tetracyclic compound 2-592 via 2-591 in an overall yield of remarkable 92%. 

The Dieckmann condensation is the intramolecular version of the Claisen condensation. 

Dieckmann Condensation The intramolecular equivalent of a Claisen condensation where dicarboxylic acid ester undergoes base-catalyzed cyclization to form a P-keto ester. 

The intramolecular version of ester condensation is called the Dieckmann condensation,119 It is an important method for the formation of five- and six-membered rings and has occassionally been used for formation of larger rings. Entries 3-6 in Scheme 2.13 are illustrative. 

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>... 

---