Active methylene component

In addition to the application of malonic esters, four-membered ring compounds can also be realized by using methyl methylsulfanylmethyl sulfoxide (14) as the active methylene component.25 27 As demonstrated in the following scheme, when the potassium salt of methyl methylsulfanylmethyl sulfoxide is allowed to react with 1,3-dibromopropane, cyclobutanone dimethyl dithioacetal 5-oxide (16) is isolated in 97% yield.8,10 Of particular interest is that the... 

Activated methylene components like malonic esters and P-ketoesters can be coupled anodically using small amounts of potassium iodide as redox catalyst (Table 4, No. 4-7) i45-i5n -pj g cathodically formed metallic potassium is used to deprotonate the methylene component generating the oxidizable carbanion. The combination of this reaction with the cathodic hydrodimerization of acrylic esters has been studied several times (Table 4, No. 7) Thus both electrode reac-... 

Two variations are worthy of mention. The alkene may be generated in situ, as for instance in the formation of the pyran from 3-bromopentane-2,4-dione. Secondly, the use of cyclic molecules as the activated methylene component leads to fused pyrans (146) and (147) from TCNE and ethyl cyanoacetate, respectively (73CB914). 

The Knoevenagel reaction can be employed for the synthesis of a wide variety of condensation products—as shown in Figure 13.54—because the carbonyl component as well as the active-methylene component can be varied. 

The stereocontroiied total synthesis of (+)-gelsemine was accomplished by T. Fukuyama and co-workers using the Knoevenagel condensation to prepare a precursor for the key divinylcyclopropane-cycloheptadiene rearrangement. The use of 4-iodooxindole as the active methylene component allowed the preparation of the (Z)-alkylidene indolinone product as a single stereoisomer. 

This carbanion certainly exists in a reversible equilibrium with both the neutral ester (XXVII) and the neutral enol (XXVIII), established by reaction of the carbanion with alcohol through the resonance forms XXV or XXVI. It is evident, however, that if the equilibrium B is not established very rapidly with inspect to A the rate of enol formation will be slower than the rate of carbanion formation. According to this interpretation, it will not be cprrccfl to say that the rate of reaction is dependent upon the rate of enoHzation of the active methylene component.14 ... 

A very large number of active methylene components and acceptor components have been used successfully.24... 

A study of the Knoevenagel condensation of cyclohexanone and benzaldehyde with three active-methylene components showed that rubidium fluoride and cesium fluoride are more effective catalysts than potassium fluoride and that lithium fluoride... 

This reaction was first reported by Emil Knoevenagel in 1894. It is a nucleophilic addition of a compound with an active methylene component to a ketone or aldehyde, followed by the elimination of water to form an olefin. Therefore, it is generally known as... 

Condensations in which the active hydrogen compound is a )3-keto ester or a )S-diketone often )deld products that result from one molecule of aldehyde or ketone and two molecules of the active methylene component. For example. 

Later that same year, Knoevenagel expanded the scope of this transformation in showing that diethylmalonate (10) could take the place of ethylacetoacetate as the active methylene component in Hantzsch s procedure, condensing with formaldehyde in the presence of diethylamine to form a bis-adduct, 11. ... 

The nitrile group is one of the most reactive electron withdrawing groups in the active methylene component, and with two nitriles, malononitrile is very reactive and condenses with almost all aldehydes and many ketones under mild conditions.Even sterically hindered ketones such as pinacolone condense with malononitrile in 48% yield using P-alanine as a catalyst. Formation of the bis-adduct is less of a problem with malononitrile than with malonic esters. 

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