3-Oxobutanoate esters, acidity alkylation

Alkyl-substituted 3-oxobutanoic and propanedioic esters can be hydrolyzed under acidic conditions to the corresponding acids, and when these are heated they readily decarboxylate (Section 18-4). Alkyl 3-oxobutanoic esters thus yield methyl alkyl ketones, whereas alkylpropanedioic esters produce carboxylic acids ... 

Ethyl 3-oxobutanoate, commonly called ethyl acetoacetate or ace tome tic ester, is much like malonic ester in that its ct hydrogens are flanked by two carbonyl groups. It is therefore readily converted into its enolate ion, which can be alkylated by reaction with an alkyl halide. A second alkylation can also be carried out if desired, since acetoacetic ester has two acidic a hydrogens. 

The anions of esters such as ethyl 3-oxobutanoate and diethyl propanedioate can be alkylated with alkyl halides. These reactions are important for the synthesis of carboxylic acids and ketones and are similar in character to the alkylation of ketones discussed previously (Section 17-4A). The ester is converted by a strong base to the enolate anion, Equation 18-18, which then is alkylated in an SN2 reaction with the alkyl halide, Equation 18-19. Usually, C-alkylation predominates ... 

The preparation of ketones via the C-alkylation of esters of 3-oxobutanoic acid (acetoacetic esters) is called the acetoacetic ester synthesis. Acetoacetic esters can be deprotonated at either the C2 or at both the C2 and C4 carbons, depending on the amount of base used. ... 

For 30 years, Raney nickel, modified with optically active compounds, has been used as an efficient heterogeneous catalyst for the reduction of 3-oxo esters such as methyl or ethyl 3-oxobutanoate. Many optically active compounds as modifiers and many supports other than Raney nickel have been tested 62 63. However, the best system by far is Raney nickel modified with tartaric acid and sodium bromide 64 6t This heterogeneous catalyst gives enantioselectivities close to 90% cc for a broad range of 3-oxo esters (Table 9). The alkyl substituents in the alcohol moiety, as well as in the 4-position of 3-oxobutanoate, can be varied without changing the enantioselectivity of 86-88% ee66. 

The second classical reaction mentioned above is the acetoacetic ester synthesis. this reaction, an ester of acetoacetic acid (3-oxobutanoic acid) such as ethyl acetoacetate is treated with base under thermodynamic control conditions and alkylated, as with the malonic ester synthesis. Reaction with sodium ethoxide in ethanol (since an ethyl ester is being used) generated the enolate and quenching with benzyl bromide led to 84. Saponification and decarboxylation (as above) gave a substituted ketone (85). Although the malonic ester synthesis and the acetoacetic ester synthesis are fundamentally similar, the different substrates lead to formation of either a highly substituted acid or a ketone. The reaction is not restricted to acetoacetate derivatives, and any p-keto-ester can be used (ethyl 3-oxopentanoate for example). ... 

---