Krapcho dealkoxycarbonylation

The mechanism of the Krapcho dealkoxycarbonylation is dependent on the structure of the substrate ester and the type of anion used. In the case of a,a-disubstituted diesters (especially the methyl esters), the anion from the salt (cyanide ion in the scheme) attacks the alkyl group of the ester in an Sn2 fashion and the decarboxylation results in the formation of a carbanionic intermediate that is quenched by the water. In the case of a-monosubstituted diesters the cyanide attacks the carbonyl group to form a tetrahedral intermediate, which breaks down to give the same carbanionic intermediate and a cyanoformate, which is hydrolyzed to give carbon dioxide and an alcohol. 

Krapcho dealkoxycarbonylation Decarboxylation of P-keto esters using alkali metal salts. 252... 

A similar dealkoxycarbonylation reaction utilizing the Krapcho conditions was used by Moberg and coworkers in the synthesis of (R)-badofen (Scheme 6.161b) from a chiral malonate precursor (see Scheme 6.52) [108],... 

Synthetic Applications of Dealkoxycarbonylation of Malonate Esters, p-Keto Esters, a-Cyano Esters and Related Compounds in Dipolar Aprotic Solvents. Krapcho, A. Synthesis, 1962, 805, 893,... 

Krapcho, A. P. Synthetic applications of dealkoxycarbonylations of malonate esters, 3-keto esters, a-cyano esters and related compounds in dipolar aprotic media. Part II. Synthesis 1982, 893-914. 

The Krapcho reaction Dealkoxycarbonylation of activated esters occurs classically under drastic thermal conditions [150], It constitutes a typical example of a very slow-reacting system (with a late TS along the reaction coordinates) and is, therefore, prone to a microwave effect. The rate-determining step involves a nucleophilic attack by a halide anion and requires anionic activation, which can be provided by solvent-free PTC conditions under the action of microwave irradiation [151, 155]. These results illustrate the difficult example of cyclic yS-ketoesters with a quaternary carbon atom in the a position relative to each carbonyl group (Eq. 64), which classically gave only 20% yield using CaCl2 in DMSO under reflux for 3 h. Some typical results are summarized in Table 4.21. 

A. P. Krapcho, Synthetic Applications of Dealkoxycarbonylations. Part II. Synthesis, 1982, 893. 

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