Knoevenagel addition reactions

Both new cascade reactions were carried out in basic medium (tertiary amines). However, the key difference of this two cascade processes is as follows. The initial reaction step in the C-glycoside formation process is a Knoevenagel condensation, whereas the chain elongation cascade starts with a Knoevenagel-addition reaction of the acyclic form of the carbohydrates. This difference is dictated by the application of either 2-hydroxypyridine (Knoevenagel-addition reaction) or proline (Knoevenagel condensation). The intermediately formed Knoevenagel addition or condensation products determinate the subsequent reaction steps. Based on that, a different outcome of these cascade reactions is observed (Scheme 2.17). 

Scheme 2.70. Asymetric domino Knoevenagel/Michael addition reaction.

C.4. Sti/le Couplings, Knoevenagel Condensations, and Michael Addition Reactions... 

On nitrided aluminophosphates, AlPON, Massinon et al. [206] observed on a series of six samples with increasing nitrogen contents a good correlation between the catalytic activity in the Knoevenagel condensation reaction and the amount of surface NH, species (1 < x < 4) quantified by the Kjeldahl method. The authors suggest that those species are not the only active species and evoke an additional role of the nitride ions in the reaction [206] on the other hand, Benitez et al. [207] suggest hydroxyls linked to aluminum cations in the vicinity of terminal P-NH2 groups as basic centers. 

The synthesis of 2,2-dimethylsuccinic acid (Expt 5.135) provides a further variant of the synthetic utility of the Knoevenagel-Michael reaction sequence. Ketones (e.g. acetone) do not readily undergo Knoevenagel reactions with malonic esters, but will condense readily in the presence of secondary amines with the more reactive ethyl cyanoacetate to give an a, /f-unsaturated cyanoester (e.g. 15). When treated with ethanolic potassium cyanide the cyanoester (15) undergoes addition of cyanide ion in the Michael manner to give a dicyanoester (16) which on hydrolysis and decarboxylation affords 2,2-dimethylsuccinic acid. 

Arsabenzaldehydes appear to be normal aromatic aldehydes26 37115. 4-Arsa-benzaldehyde (36) undergoes the Aldol and Knoevenagel as well as a variety of typical aldehyde addition reactions 37,115). 

Both 1,3- and 1,4- bis[2-(2-arylethenesulfonyl)vinyl]benzenes, synthesized by a Knoevenagel reaction between the appropriate benzenedicarbaldehyde and 2-arylethenesulfonylacetic acid, behave as Michael acceptors and undergo double Michael addition reactions with activated methylene compounds. The products are phenylene-bis(tetrahy-drothiopyran 1,1-dioxides) 460 (Scheme 158) <2005JHC255>. 

II. The formation of afi-unsaturated carbonyl compounds, in which the initial addition reaction is followed by dehydration (Perkin, Knoevenagel, and Claisen-Schmidt condensations). 

In the next two sections we will concentrate on the catalytic activity of basic zeolites and mesoporous molecular sieves in the Knoevenagel condensation and Michael addition reactions. 

Aramendia, MA Borau. V Jimenez, C Marinas, JM Romero. FJ. New aspects of Knoevenagel condensation and Michael addition reactions on alkaline carbonates. Chemisrrv Letters 2000 514-575. 

Based on a domino Knoevenagel/cne reaction, Tietze and Steinmetz developed a stereoselective solid-phase synthesis of cyclopentane and cyclohexane derivatives of type 326 and 327 using a Merrifield resin modiiled with a propandiol linker 320 as shown in Scheme 4.6.3. Subsequent reaction with monomethyl malonoyl chloride 321 afforded the polymer-bound malonate 322, which, in a two-component domino reaction was treated with unsaturated aldehydes 323 in the presence of a catalytic amount of piperidinium acetate and zinc chloride. Except for a-substituted aldehydes, the initial Knoevenagel condensation occurred without addition of dehydrating agents and the subsequent intramolecular ene reaction gave cyclopentane and cyclohexane derivatives 325 after cleavage firom the resin either by reduction or transesterification. 

Heteroatom conjugate addition reactions are promoted by superbases. Draper et al. described the synthesis of the estrogen antagonist Sch 57050 (179) [53]. Knoevenagel condensation reaction with ketone 176 and aldehyde 177 in the presence of piperidine... 

The product from the addition of an enolate of a 1,3-dicarbonyl-type compound with an aldehyde (or ketone) dehydrates readily to give the a,(3-unsaturated dicarbonyl product. This is known as the Knoevenagel condensation reaction, typically carried out under mild conditions with an amine base, and is a useful method for the formation of alkenes bearing electron-withdrawing substituents (see Section 1.1.3). 

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