Tandem reactions Knoevenagel reaction

A more recent application of the Knoevenagel reaction is its use in domino reactions. The term domino reaction is used for two or more subsequent transformations, where the next reaction step is based on the functionality generated in the preceding step. Such reactions are also called tandem reactions or cascade reactions. 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

The tandem-Knoevenagel-ene reaction is a powerful tool to synthesize five-and six-membered carbocycles.2 5 The process is exemplified by the diastereoselective synthesis of 4a. Compound 4a has been obtained In both enantiomeric forms and as a racemate according to the procedure described here. The sequence includes the Knoevenagel reaction of citronellal, 1, and dimethyl malonate, 2, followed by the intramolecular ene cyclization of the chiral 1,7-diene 3 to yield the trans 1,2-disubstituted products 4a and 4b. Whereas the thermal cyclization of 3 at 160°C provides 4a and 4 b in a ratio of only 89.7 10.3, the Lewis acid... 

Scheme 6.144 Thiochromanes prepared from the 121-catalyzed enantioselective tandem Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and diethyl methylenemalonates. The product configurations were not determined.

Tandem Passerini/Knoevenagel reactions were also performed by employing 2-nitrophenylacetic acid as the acid component to give the butenolides 65 that were reduced to the intermediate amines 66, which immediately cyclized to give indoles 67 in very high yields via a ring-switching process (Scheme 2.24) [52],... 

We have been particularly enamored with the development of experiments involving carbon-carbon bond formation, especially as part of tandem reactions occurring in a single container (see the Diels-Alder reaction. Figure 1). One such reaction is the synthesis of simple esters of coumarin-3-carboxylic acids via a Knoevenagel condensation between malonic esters and various a-hydroxybenzaldehydes, followed by intramolecular nucleophilic acyl substitution. This conversion, catalyzed by piperidine, has been carried out under a variety of conditions, for example, at room temperature without solvent... 

M. N. Elinson, R. F. NasybuUin, G. I. Nikishin, C. R. Chim. 2013, 16, 789-794. Sodium acetate catalyzed tandem Knoevenagel-Michael multicomponent reaction of aldehydes, 2-pyrazolin-5-ones, and cyano-functionalized C-H acids facile and efficient way to 3-(5-hydroxypyrazol-4-yl)-3-aryl-propionitriles. 

Keywords Salicylic aldehydes, malononitrile, cyclic secondary amines/thiols, sodium formate, ethanol, room temperature, one-pot multicomponent reaction, tandem Knoevenagel-cyclocondensation, benzopyrano[2,3- f pyrimidmes/2-amino-4-arylsulfanyl-4//-chromene-3-corbonitriles... 

Scheme 2.30 Tandem Michael-Morita-Baylis-Hillman -Knoevenagel reaction catalysed by a chiral diarylprolinol trimethylsilyl ether and L-proline.

Aqueous solutions of hydrotropes (e.g. NaBMGS, sodium methylcello-solve sulfate) have been used in the Hantzsch dihydropyridine synthesis, a tandem Knoevenagel and Michael reaction, in which acetoacetic ester reacts with benzaldehydes and methyl aminocrotonate or aqueous ammonia at room temperature or heated with microwaves (MW) [16,17] ... 

More than the corresponding enolexo-aldolizations, amine-catalyzed 6-enolmdo aldol reactions have frequently been used synthetically. An early example is the synthesis of Hagemaris ester (89) from formaldehyde and acetoacetate via piperidine-catalyzed Knoevenagel-Michael-aldol tandem-reaction follo ved by decarboethoxylation (Scheme 4.14, Eq. (1)) [83]. Related product 91 vas obtained vhen thiophene-carbaldehyde 90 vas used (Eq. (2)) [84]. 

Tandem sequences involving Knoevenagel condensation followed by electrocyclization have not been employed as extensively as other tandem reactions (such as the tandem Knoevenagel-Diels-Alder reaction), but have been used in a few cases with great success, rapidly constructing complex polycyclic cores. 

An one-pot convenient method for the synthesis of a variety of 2,2 -dicyanoalkylphosphonates (557) by a tandem Knoevenagel-phospha-Michael reaction of triethyl phosphite (556) with aryl/heteroaryl/alkyl aldehydes (554) and malonitrile (555) in an aqueous micellar solution of sodium stearate,using surfactants, such as cetyltrimethylammonium bromide as a eationic mieelle and TritonX-100 as a neutral micelle at their critical micellar eoncentrations (CMC), has been described by Sobhani and Parizi (Scheme 138). ... 

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