Condensation reactions conjugate addition

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

The following reaction involves a conjugate addition reaction followed by an intramolecular Claisen condensation. Write both steps, and show their mechanisms. 

CIDNP 874, 879, 1070 Claisen-type condensation 259 a-Cleavage, photochemical 875-877 Conjugate addition reactions 778, 783-785, 788... 

The mechanism of the cyanide- and thioazolium ion-catalyzed conjugate addition reactions is considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation. Thus the cyano-stabilized carbanion resulting from deprotonation of the cyanohydrin of the aldehyde is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, cyanide is eliminated to form the product and regenerate the catalyst. 

The same type of reaction has been applied to the preparation of 1,2-dihydroquinoline-3- and 277-l-benzothiopyran-3-carboxylic acid derivatives (equation 38) via a magnesium amide-induced sequential conjugate addition-aldol condensation reaction between 2-(alkylamino)phenylketones or 2-mercaptobenzophenones . 

This is an example of a Robinson annulation. The mechanism for the Robinson annulation involves a sequence of conjugate addition reactions and aldol condensations. As illustrated, the first step is deprotonation of cyclohexanedione with sodium hydride. The resulting anion then participates in a 1,4-addition to methyl vinyl ketone. The resulting enolate anion then tautomerizes through... 

Bunce, R. A., Harris, C. R. Six-membered cyclic (i-keto esters by tandem conjugate addition-Dieckmann condensation reactions. J. Org. Chem. 1992, 57, 6981-6985. 

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... 

A popular and useful application of the conjugate addition reaction is the combined conjugate addition-intramolecular aldol strategy, commonly known as the Robinson annulation. When the Michael donor is a ketone and the Michael acceptor an a,p-unsaturated ketone, the product is a 1,5-diketone which can readily undergo cyclization to a six-membered ring. Typical Michael donor substrates are 2-substituted cyclohexanones, which condense with alkyl vinyl ketones to give the intermediate conjugate addition products 42 (1.52). The subsequent intramolecular... 

Asymmetric conjugate addition reactions of carbonyl compounds with a, -unsaturated systems are known. The simple amine a-methylbenzylamine 68 acts as both the activator (to give the imine and hence the enamine required for alkylation) and as the chiral auxiliary to effect neutral asymmetric conjugate-addition reactions. " Thus, condensation of (5)-a-methylbenzylamine 68 with 2-methylcyclohexanone, followed by addition of methyl acrylate (and hydrolysis of the product imine), gave the 2,2-disubstituted cyclohexanone 69 with high enantiomeric purity (1.78). 

Condensation and Conjugate Addition Reactions of Carbonyl Compounds More... 

Conjt te addition reactions involve a nucleophile, which is often an enolate, adding to the /3 position of an a,j8-unsaturated carbonyl compound. One of the most common conjugate addition reactions is the Michael addition. As we shall see, the aldol condensation provides a way to synthesize a,j8-unsaturated carbonyl compounds that we can then use for subsequent conjugate addition reactions. 

CHAPTER 19 CONDENSATION AND CONJUGATE ADDITION REACTIONS OF OARBONYL COMPOUNDS... 

Thus far we have only considered examples of aldol reactions where the reactant forms a product by dimerization. In the coming sections we shall discuss the use of aldol reactions to more generally prepare j8-hydroxy and a,j8-unsaturated carbonyl compounds. We shall then study reactions called conjugate addition reactions (Section 19.7), by which we can further build on the a,/3-unsaturated carbonyl systems that result from aldol condensations. 

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