P-keto acid decarboxylation

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... 

Wasserman, H.H. in Newman Steric Effects in Organic Chemistry, Wiley NY, 1956, p. 352. See also Buchanan, G.L. Kean, N.B. Taylor, R. Tetrahedron, 1975, 31, 1583. StericaUy hindered P-keto acids decarboxylate more slowly Meier, H. Wengenroth, H. Lauer, W. Krause, V. Tetrahedron Lett., 1989, 30, 5253. 

Sterically hindered p-keto acids decarboxylate more slowly Meier Wengenroth Laucr Krause Tetrahedron... 

Sterically hindered P-keto acids decarboxylate more slowly Meier, H. Wengenroth, H. Lauer, W. Krause, V. Tetrahedron Lett. 1989, 30, 5253. 

P-Keto acids, decarboxylation, 762—763, 768, 838, 840-841, 850 Keto-enol isomerism, 355, 705—707 Keto-enol tautomerism. See Keto-enol isomerism P-Keto esters acidity of, 831 alkylation of, 839-841, 850 Michael addition of, 846—847 nomenclature of, 832 preparation of... 

PROBLEM 18.46 We learned in Chapter 17 that most P-keto acids decarboxylate very easily (p. 858). The compound below is an exception, as it survives heating to very high temperature without losing carbon dioxide. Explain. 

Decarboxylation (Section 22.7) The loss of carbon dioxide from a molecule. p-Keto acids decarboxylate readily on heating. 

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... 

Section 19 17 11 Dicarboxylic acids (malonic acids) and p keto acids undergo thermal decarboxylation by a mechanism m which a p carbonyl group assists the departure of carbon dioxide... 

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... 

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... 

Here too there is an enol that tautomerizes to the product. The mechanism is illustrated for the case of P-keto acids, ° but it is likely that malonic acids, a-cyano acids, a-nitro acids, and P,y-unsaturated acids behave similarly, since similar six-membered transition states can be written for them. Some a,P-unsaturated acids are also decarboxylated by this mechanism by isomerizing to the p,y-isomers before... 

For a review of the mechanism of the decarboxylation of P-keto acids, see Jencks, W.P. Catalysis in Chemistry and Enzjnology, McGraw-Hill NY, 1969, p. 116. 

Figure 5.8 Examples of formation and cleavage of carbon-carbon bonds (a) aldol condensation, (b) Claisen ester condensation and (c) decarboxylation of a P-keto acid. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

The mechanistic steps can be deduced by inspection of structures and conditions. Enolate anion formation from diethyl malonate under basic conditions is indicated, and that this must attack the epoxide in an Sn2 reaction is implicated by the addition of the malonate moiety and disappearance of the epoxide. The subsequent ring formation follows logically from the addition anion, and is analogous to base hydrolysis of an ester. Ester hydrolysis followed by decarboxylation of the P-keto acid is then implicated by the acidic conditions and structural relationships. 

Decarboxylation is the loss of Ccirbon dioxide, which happens easily because of the stability of CO2. Heating P-keto acids to between 100 and 150 degrees Celsius is one example of a decarboxylation reaction. The mechanism for the decarboxylation of a P-keto acid is in Figure 12-43. 

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. 

You may have already come across the importance of six-membered ring transition states in organic chemistry, e.g. in the decarboxylation of P-keto acids (Scheme 5.14). 

Catalytic decarboxylation processes occur in aliphatic keto acids in which the keto group is in an a-position to one carboxyl group and in a P-relationship to another. Thus, the normal decarboxylation of a p-keto acid is facilitated by metal coordination to the a-keto acid moiety. The most-studied example is oxaloacetic acid and it has been shown that its decarboxylation is catalyzed by many metals following the general order Ca2+ < Mn2+ < Co2+ < Zn2+ < Ni2+ < Cu2+ < Fe3+ < Al3"1".66 67 The overall rate constants can be correlated with the stability constants of 1 1 complexes of oxalic acid rather than oxaloacetic acid, as the uncoordinated carboxylate anion is essential for the decarboxylation. The generally accepted mechanism is shown in Scheme 15. Catalysis can be increased by the introduction of x-bonding ligands, which not only increase the... 

The compounds most frequently encountered in this reaction are 3-keto acids, that is, carboxylic acids in which the p carbon is a carbonyl function. Decarboxylation of p-keto acids leads to ketones. 

An earlier series of experiments established useful synthetic transformations involving carboxylation of ketones and nitroalkanes to yield P-keto acids and a-nitro acids respectively (Scheme 94).362 363 The reagent is methylmagnesium carbonate and the intermediate (130) can be alkylated with concomitant decarboxylation to provide greater versatility. These reactions can also be extended to ketone functions in imidazoline- and oxazolidine-diones (Scheme 95).364,365... 

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