Knoevenagel-type reactions

Tellurium tetrachloride is an efficient catalyst in the Knoevenagel reaction of non-enoUz-able aldehydes with active methylene compounds.  

Typical procedure. A mixture of the carbonyl compound (0.01 mol), the active methylene compound (0.01 mol) and tellurium(lV) tetrachloride (0.001 mol) was thoroughly mixed at room temperature. After being stirred for 5 min, the mixture was heated and continuously stirred at 80°C in an oil bath (20-75 min). The reaction was cooled at room temperature and treated with a solution of 1% aqueous alcohol. The product was extracted with methylene chloride, washed with water. After drying over Na2S04 the solvent was removed in vaccuo over rotatory evaporator to obtain the product in high purity. 

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An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

Aldehydes and ketones condense with a-halo esters in the presence of bases to give ot,p-epoxy esters, called glycidic esters. This is called the Darzens condensation. The reaction consists of an initial Knoevenagel-type reaction (16-41), followed by an internal Sn2 reaction (10-13) ° ... 

Hayashi et al. have reported a novel Knoevenagel-type reaction with titanium enolate 70 derived from diketene 69 as the C4 unit source (Scheme 26).76 In contrast to the conventional Knoevenagel reaction (basic conditions), this transformation proceeds under mildly acidic conditions and provides higher yields and better E Z ratios. 

Hayashi, M., Nakamura, N., Yamashita, K. Novel Knoevenagel-type reaction via titanium enolate derived from Ti(0-i-Pr)4 and diketene. 

Simple aliphatic thioketones (6) readily condense with active methylene compounds in a Knoevenagel-type reaction (Scheme 11). The reaction in Scheme 11 proceeds more easily than with ketones, often without catalysts, and involves nucleophilic attack by the X(NC)HC moiety. 

A domino reaction of an aldehyde (R -CHO) with nitromethane followed by a second aldehyde (R -CH2CHO) yields a functionalized two-stereocentre product (74). Using a simple proline derivative, diphenylprolinol TMS ether, des typically over 95% and ees of 99% were obtained. This amine serves as a multiple-hydrogen-bond-donor (MHBD) catalyst, and is proposed to act in iminium mode for the Knoevenagel-type reaction of nitromethane ion, and then as an enamine catalyst of the second step. ... 

The current proposal for assembly of the carbon skeleton of lycopodine (27) [55] is as shown in Scheme 13 bottom. 4-(2-Piperidyl)-3-oxobutanoate (29) is the central intermediate in this scheme. This material may suffer decarboxylation yielding pelletierine (28) which is incorporated into the C-9 to C-16 fragment. The keto group at C-15 (lycopodine numbering) of that fragment is then condensed in a Knoevenagel type reaction with the methylene group of the -keto acid function of 4-(2-piperidyl)-3-oxobutanoate to form the C-15 to C-8 bond. 

Condensation of aldehydo-pentose derivatives with cyanomethyl-phosphonate esters in a Knoevenagel type reaction led to the... 

The Pummerer- and Knoevenagel-type reactions of ben l sulfide with 1,3-dicarbonyl compounds in the presence of o-chloranil were achieved by Z. Li et al. (Scheme 8.32). ... 

Scheme 8.32 o-Chloranil-mediated Pummerer- and Knoevenagel-type reactions. 

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