Condensation reactions, carbonyl compounds alkylation, enolate ions

The photostimulated arylation of ketone enolate ions has been shown to be of fairly wide scope, although the reaction fails with the enolate ions of acetophenone and several -dicarbonyl compounds and is impeded by steric crowding. Coupled with new, mild methods for the regeneration of the carbonyl group (see Section 4), the chemistry of azomethine ketone derivatives has taken on new dimensions. The alkylation of such derivatives has been of particular interest recently. For example, two groups of workers have shown that only yn-dianions are formed on metalation of oximes. Furthermore, the dianions are configurationally stable, allowing alkylation and aldol condensation to be effected stereo-specifically (Scheme 22). - . 

There is no simple answer to this question, but the exact experimental conditions usually have much to do with the result. Alpha-substitution reactions require a full equivalent of strong base and are normally carried out so that the carbonyl compound is rapidly and completely converted into its enolate ion at a low temperature. An electrophile is then added rapidly to ensure that the reactive enolate ion is quenched quickly. In a ketone alkylation reaction, for instance, we might use 1 equivalent of lithium diisopropylamide (LDA) in lelrahydrofuran solution at -78 °C. Rapid and complete generation of the ketone enolate ion would occur, and no unreacled ketone would be left so that no condensation reaction could take place. We would then immediately add an alkyl halide to complete the alkylation reaction. 

A large number of reactions have been presented in this chapter. However, all of these reactions involve an enolate ion (or a related species) acting as a nucleophile (see Table 20.2). This nucleophile reacts with one of the electrophiles discussed in Chapters 8, 18, and 19 (see Table 20.3). The nucleophile can bond to the electrophilic carbon of an alkyl halide (or sulfonate ester) in an SN2 reaction, to the electrophilic carbonyl carbon of an aldehyde or ketone in an addition reaction (an aldol condensation), to the electrophilic carbonyl carbon of an ester in an addition reaction (an ester condensation) or to the electrophilic /3-carbon of an a,/3-unsaturated compound in a conjugate addition (Michael reaction). These possibilities are summarized in the following equations ... 

---