Enolate compounds carbon nucleophile coupling

The aldol reaction is one of the most important approaches for selective carbon-carbon bond formation in organic synthesis [94]. This transformation can be achieved by conversion of one carbonyl group into a silylated enol derivative, followed by nucleophilic coupling to another carbonyl compound with the aid of a Lewis acid, for example, TiCU (Scheme 14.29). 

It is also important to realize that the construction of the (3-keto ester function in VI, whose predictable role as a stabilized carbanion can be exploited to build the carbocycle, requires the consolidation of a C-C bond between C-6 of compound I and a methyl acetate unit from II. This task cannot be accomplished without a preliminary step, since the carbons involved are hardly active in the nucleophilic sense at the outset. This prior step consists of the coupling of I and II as the consequence of the nucleophilic character of the enol ether fragment of I and the strongly electrophilic nature of the triple bond of II. The result would be zwitterion V (see Scheme 38.1). 

The original Mannich reaction is the acid-catalyzed aminomethylation of enohz-able ketones with non-enolizable aldehydes and ammonia, primary amines, or secondary amines, which involves nucleophilic addition of ketone enols to iminium salts generated in situ from the aldehydes and the nitrogen compounds [183]. This three-component coupling reaction provides a powerful tool for carbon-carbon bond formation and introduction of nitrogen functionality. The classical Mannich reaction has some drawbacks in reaction efficiency, regioselectivity, and appli-... 

The aldol reaction involves the substitution of an ct-hydrogen by the carbonyl carbon of another carbonyl compound, thereby creating a 3-hydroxycarbonyl product. Eq. 11.13 shows the coupling of two aldehydes, while Eq. 11.14 shows the coupling of two ketones. The reaction is similar to the alkylation and halogenation of an enolate, except that now the electrophile is another carbonyl compound, and so we have nucleophilic addition to a carbonyl as well as substitution on an a-carbon. As with other reactions we have seen in this section, the aldol reaction can proceed via an enol or an enolate. However, the most common pathway, and the one we will emphasize here, makes use of an enolate and so is base-catalyzed. With prolonged treatment in acid or base, the p-hydroxycarbonyl products will dehydrate to form a,(3-unsaturated carbonyl structures. 

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