Decarboxylation of P-keto ester

P-Keto acids484 are easily decarboxylated, but such acids are usually prepared from p-keto esters, and the esters are easily decarboxylated themselves on hydrolysis without isolation of the acids.485 This decarboxylation of p-keto esters involving cleavage on the carboxyl side of the substituted methylene group (arrow) is carried out under acidic, neutral, or... 

Nucleophilic cleavage is especially useful for initiating the decarboxylation of P-keto esters and malonates without the retro-Claisen competition that frequently attends traditional base-catalysed hydrolysis [Scheme 6.7].27>2S In the case of malonates, only one of the ester functions is cleaved.29 A P-carbonyl group is... 

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

As is true in other groups of secondary metabolites, several types of reactions follow the initial cyclizations addition and removal of hydroxyl and methoxyl groups, oxidation of methyl groups to alcohols, aldehydes, and acids, the reverse of this series, and decarboxylation. Decarboxylation of p-keto esters is especially common. 

Decarboxylation of P-keto-esters is facile in aqueous DMSO, but in less reactive cases decarboxylation is accelerated by sodium chloride. Condensation reactions of dibenzocycloheptadienone (334) with aromatic aldehydes have been reported. Syntheses of the heterocyclic carboxylic acids (335) have been described. No effect of the heterocycle s ring current on the chemical shifts of the methylene protons could be detected in the n.m.r. spectrum of the nonamethylene-thiadiazine dioxide (336), which was prepared from cyclododecane-l,3-dione. ... 

Scheme 5.122 Enantioselective protonation of chiral palladium enolates generated by decarboxylation of p-keto esters 487 and 489 simplified proposed catalytic cycle.

Kukula P, Matousek V, Mallat T, Baiker A. Enantioselective decarboxylation of P-keto esters with Pd/amino alcohol systems successive metal catalysis and organocatalysis. Chem. Eur. J. 2008 14 2699-2708. 

Miscellaneous Reactions. Alcohols, including tertiary ones, can be converted to their acetoacetates by reaction with Diketene in the presence of DMAP at it. Decarboxylation of p-keto esters has been carried out at pH 5-7 using 1 equiv of DMAP in refluxing wet toluene (eq 5). ... 

The thermal decarboxylation of p keto acids is the last step in a ketone synthesis known as the acetoacetic ester synthesis The acetoacetic ester synthesis is discussed in Section 21 6... 

The major application of p keto esters to organic synthesis employs a similar pat tern of ester saponification and decarboxylation as its final sfage as described m fhe fol lowing secfion... 

Section 21 5 Hydrolysis of p keto esters such as those shown m Table 21 1 gives p keto acids which undergo rapid decarboxylation forming ketones... 

The majority of publications on transesterification catalyzed by solid acids have focused on the reaction of 3-keto esters. Transesterification provides an alternative route to synthesize these kinds of esters since direct preparation from P-keto acids is not a good option given that they can easily undergo decarboxylation. Table 11 provides a review of results in the literature relating to the transesterification of P-keto esters with alcohols. 

When p-keto esters are treated with concentrated base, cleavage occurs, but is on the keto side of the CR2 group (arrow) in contrast to the acid cleavage mentioned on page 838. The products are a carboxylic ester and the salt of an acid. However, the utility of the reaction is somewhat hmited by the fact that decarboxylation is a side reaction, even under basic conditions. p-Diketones behave similarly to give a ketone and the salt of a carboxylic acid. With both p-keto esters and p-chketones, OEt can be used instead of OH, in which case the ethyl esters of the corresponding acids are obtained instead of the salts. In the case of p-keto esters, this is the reverse of Claisen condensation (16-85). The similar cleavage of cychc a-cyano... 

The alkylation of p-keto ester enolates followed by decarboxylation affords substituted ketones (acetoacetic ester synthesis). The ester group acts as a temporary activating group. Retro-Claisen condensation can be a serious problem during hydrolysis of the ester, particularly in basic solution if the product has no protons between the carbonyl groups. In these cases, the hydrolysis should be carried out under acidic conditions or using one of the methods of decarbalkoxylation described in the next section. 

These carbanions can be formed (Figure 5.8) by proton abstraction from ketones resulting in aldol condensations, by proton abstraction from acetyl CoA, leading to Claisen ester condensation, and by decarboxylation of p-keto acids leading to a resonance-stabilised enolate, which can likewise add to an electrophilic centre. It should be noted that the reverse of decarboxylation also leads to formation of a carbon—carbon bond (this is again a group transfer reaction involving biotin as the carrier of the activated CO2 to be transferred). 

Lhommet and coworkers prepared the chiral bicyclic carbamate 1189 from L-lysine by a method that involved an electrochemical methoxylation (Scheme 150). ° This precursor, in effect a disguised acyliminium ion, reacted with the sdylated enol 1190 and trimethylsilyl triflate to give a diaste-reomeric mixture of p-keto esters (+)-1191, hydrolysis and decarboxylation of which produced ketone (—)-1192 as the only discernible product. It was essential to reduce this ketone stereoselectively in order to set up the configuration of the target alkaloid s side chain correctly. Fortunately, this was achieved with either K-Selectride or with lithium triethylborohydride. 

These substances, as well as the parent compound, are p-keto esters and undergo hydrol3rtio cleavage in two directions. One type of cleavage, ketonlc hydrolysis, is effected by the action of dilute caustic alkali in the cold, followed by acidification and boiling the free acetoacetic acid produced has a carboxyl and carbonyl group on the same carbon atom and therefore readily undergoes decarboxylation to yield a ketone, for example ... 

Suggestions as to the methods for identifying the above classes of compounds will be found under Class Reactiona in Section XI,7. Some fimther remarks upon enolic compounds (see Table IV,1I4A) may be made here. Enols may be divided into (a) p-keto esters and (b) 1 3-diketones. With 5 per cent, sodium hydroxide solution, a p-keto ester yields the salt of the corresponding acid, which when heated with dilute hydrochloric acid is decarboxylated to a ketone ... 

The carbon-carbon bond forming potential inherent m the Claisen and Dieckmann reac tions has been extensively exploited m organic synthesis Subsequent transformations of the p keto ester products permit the synthesis of other functional groups One of these transformations converts p keto esters to ketones it is based on the fact that p keto acids (not esters ) undergo decarboxylation readily (Section 19 17) Indeed p keto acids and their corresponding carboxylate anions as well lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation... 

The sequence begins with a Claisen condensation of ethyl pentanoate to give a p keto ester The ester is hydrolyzed and the resulting p keto acid decarboxylates to yield the desired ketone... 

The anion of a p keto ester may be alkylated at carbon with an alkyl halide and the product of this reaction subjected to ester hydrolysis and decarboxylation to give a ketone... 

Esters are hydrolysed under basic conditions in the presence of quaternary ammonium salts [e.g. 1-7], Microwave activation of basic soliddiquid systems without an added solvent enhances the rate of saponification and the reaction is not affected by steric factors [3], Microwave irradiation has also been used in the hydrolysis and decarboxylation of malonic esters [8] and p-keto esters [9] (>90%). Lactones... 

Method D (hydrolysis and decarboxylation of malonic esters and fi-keto esters) LiBr (1.73 g), TBA-Br (0.32 g, 1 mmol), the malonic ester or p-keto ester (10 mmol) and H20 (360 ml) are subjected to microwave irradiation for 15 min. The cooled mixture is extracted with EtOAc (50 ml) and the organic solution is filtered through Florisil and evaporated to yield the decarboxylated compound. 

Ethyl 3-oxoalkanoates when not commercially available can be prepared by the acylation of tert-butyl ethyl malonate with an appropriate acid chloride by way of the magnesium enolate derivative. Hydrolysis and decarboxylation in acid solution yields the desired 3-oxo esters [59]. 3-Keto esters can also be prepared in excellent yields either from 2-alkanone by condensation with ethyl chloroformate by means of lithium diisopropylamide (LDA) [60] or from ethyl hydrogen malonate and alkanoyl chloride usingbutyllithium [61]. Alternatively P-keto esters have also been prepared by the alcoholysis of 5-acylated Mel-drum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione). The latter are prepared in almost quantitative yield by the condensation of Meldrum s acid either with an appropriate fatty acid in the presence of DCCI and DMAP [62] or with an acid chloride in the presence of pyridine [62] (Scheme 7). 

The submitters state that ethyl enanthylsuccinate can be hydrolyzed and decarboxylated to 7-oxocapric acid. The reaction is carried out by heating 57 g. of the keto ester with a solution of 140 ml. of concentrated sulfuric acid in 250 ml. of water. The mixture is stirred while the ethanol is removed gradually by distillation over a period of 3 hours. The acid is taken up in benzene, extracted from the benzene with aqueous alkali, and liberated from the alkaline solution by acidification with concentrated hydrochloric acid. After recrystallization from 50% ethanol about 29 g. (78% yield) of 7-oxocapric acid is obtained as colorless crystals, m.p. 69-70°. 

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