3-Ketocarboxylic 7-alkylation ketones

Allyl esters of acetoacetates7-8-9-11 react with Pd° catalysts to generate initially a bisphosphine allylpal-ladium cation, with the 3-ketocarboxylate serving as counterion. Under the reaction conditions the (3-ketocarboxylate decarboxylates, yielding a -Tr-allylpalladium ketone enolate complex. The required nucleophile is thus formed in situ and is capable of Pd-mediated alkylation. A wide spectrum of reactions have been based on this chemistry which will be discussed in later sections. 

Fig. 13.29. Synthesis of complicated ketones in analogy to the acetoacetic ester synthesis II generation of a cyclic ketone. In the first step, the /3-ketoester is alkylated at its activated position. In the second step, the /3-ketoester is treated with Li I . SN2 reaction of the iodide at the methyl group generates the /3-ketocar-boxylate ion as the leaving group. The /3-ketocarboxylate decarboxylates immediately under the reaction conditions (temperature above 100 °C) and yields the enolate of a ketone.

The butylated /3-ketoester C of Figure 10.23 is not the final synthetic target of the acetoacetic ester synthesis of methyl ketones. In that context the /3-ketoester C is converted into the corresponding /3-ketocarboxylic add via add-catalyzed hydrolysis (Figure 10.24 for the mechanism, see Figure 6.19). This /3-ketocarboxylic acid is then heated either in the same pot or after isolation to effect decarboxylation. The /3-ketocarboxylic add de-carboxylates via a cyclic six-membered transition state in which three valence electron pairs are shifted at the same time. The reaction product is an enol, which isomerizes immediately to a ketone in general and to phenyl methyl ketone in the specific example shown. In general, alkyl methyl ketones are obtained by such acetoacetic ester syntheses. 

Synthesis of ketones from /3-ketocarboxylic acid esters Alkylation of /i-ketocarboxylic acid esters s. 4, 776... 

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