Chain-Elongating Syntheses of Carbonyl Compounds

2 Alkylation of Quantitatively Prepared Enolates and Aza-enolates Chain-Elongating Syntheses of Carbonyl Compounds and Carboxylic Acid Derivatives 

All the reactions discussed in this section are SN2 reactions with respect to the alkylating reagent. The most suitable alkylating reagents for enolates and aza enolates are therefore the most reactive alkylating reagents (Section 2.4.4), that is, Mel, Rpr/m—X, and especially H2C=CH—CH2—X and Ar—CH2—X (X = Hal, OTs, OMs). Isopropyl bromide and iodide also can alkylate enolates in some instances. Analogous compounds Rsec—X and R(ert—X either do not react with enolates at all or react via E2 eliminations to afford alkenes. 

Ester-substituted ketone enolates are stabilized, and these enolates can be alkylated (ace-toacetic ester synthesis). Alkylation is, however, also possible for enolates that are not stabilized. In the case of the stabilized enolates, the alkylated ketones are formed in two or three steps, while the nonstabilized enolates afford the alkylated ketones in one step. However, the preparation of nonstabilized ketone enolates requires more aggressive reagents than the ones employed in the acetoacetic ester synthesis. 

The quantitative conversion of aldehydes into enolates with lithium amides hardly ever succeeds because an aldol reaction (cf. Section 13.1.2) occurs while the deprotonation with LDA is in progress. Aldol additions also occur upon conversion of a small fraction of the aldehyde into the enolate with a weak base (Section 13.3.1). Hence, it is generally impossible to alkylate an aldehyde without the simultaneous occurrence of an aldol addition. There is only one exception certain a-branched aldehydes can be deprotonated to their enolates in equilibrium reactions, and these enolates can be reacted with alkylating reagents to obtain tertiary aldehydes. 

The obviously low electrophilicity of the C=N double bonds of aldimines precludes the addition of the azaenolate to remaining aldimine in the course of aldimine deprotonation. The aldimine enolate is obtained quantitatively and then reacted with the alkylating reagent. This step results cleanly in the desired product, again because of the low electrophilicity of imines as the alkylation progresses, azaenolate and the alkylation product coexist without reacting with each other, no aldol-type reaction, no proton transfer. All the azaenolate is thus converted 

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