Enolate ions stabilization energy

Carbonyl compounds are more acidic than alkanes for the same reason that carboxylic acids are more acidic than alcohols (Section 20.2). In both cases, the anions are stabilized by resonance. Enolate ions differ from carboxylate ions, however, in that their two resonance forms are not equivalent—the form with the negative charge on oxygen is lower in energy than the form with the charge on carbon. Nevertheless, the principle behind resonance stabilization is the same in both cases. 

Under the conditions of most alkylation reactions, the products of O- and C-alkylation are usually not interconvertible, so it is not valid to predict C-alkylation directly on the basis of thermodynamic considerations. But, the transition state B and D resemble the products C and E, respectively, to a significant extent. It is therefore expected that the transition state for C-alkylation will be lower in energy, anticipating to some extent the greater stability of the product. This is depicted in Figure 1.2. The competition between O- and C-alkylation will then depend upon the interplay among (1) solvation effects, (2) nucleophilicity of the C and O ends of the enolate ion, and (3) transition-state structure. 

Why do stabilized anions undergo 1,4- rather than 1,2-addition to Michael acceptors 1,2-Addition occurs, but is reversible with relatively stable anionic nucleophiles, because it leads to a relatively high-energy alkoxide. Conjugate addition is favored thermodynamically because it produces a resonance-stabilized enolate ion. 

The Mg ion stabilizes the enolate anion intermediate by coordination with the negatively charged oxygen. Stabilization of the enolate lowers the energy of the transition state, increasing the rate of the reaction. 

Ab initio Hartree-Fock calculations of the stabilities of enols and carbonyl compounds (Table 5) have been performed in recent years by Hehre and Lathan (1972), Bouma et al. (1977, 1980 see also Bouma and Radom, 1978a,b) and Noack (1979). The order or magnitude of the differences in energies (AE) is the same as that estimated for acetone in the gas phase (AG = 13.9 + 2 kcal mol-1 at 25 °C) by Pollack and Hehre (1977) from an ion cyclotron resonance spectroscopy study of the proton and deuteron transfers from CD3C(OH)CD to aniline. This gave relative values for the O—H and... 

Alkyl anions have been implicated as intermediates stabilized by a neutral molecule. Alkoxide ions when photolysed in a pulsed ICR spectrometer dissociate into alkanes and enolate anions The intermediate 19 in equation 25 can be represented by two possible extremes. In 19a the alkyl anion R is solvated by a ketone and inl9b the radical anion of the ketone is solvated by the radical R. The structure of this intermediate will then depend on the relative electron affinities of the alkyl group R and the ketone. Brauman and collaborators photolysed a series of 2-substituted-2-propoxides (18 with R = CH3, R" = H and R varied). For substituents R = CF3, H, Ph and H2C=CH, the C—R bond dissociation energies for homolytic fission are larger than the C—CH3 bond energy, i.e. if the intermediate complex has the structure 19b then methane would be expected to be produced. Conversely, since these R groups form more stable anions than CH3, decomposition via 19a should result in RH. The experimental observation that only RH is formed led to the conclusion that 19 is best described by the solvated alkyl anion structure 19a. 

Notice that the last step in the mechanism is deprotonation of the P-keto ester to give a doubly stabihzed enolate. This deprotonation step cannot be avoided, because the reaction occurs under basic conditions. Each molecule of base (alkoxide ion) is converted into the doubly stabihzed enolate, which is a favorable transformation (downhill in energy). In fact, the deprotonation step at the end of the mechanism provides a driving force that causes the equihbrium to favor condensation. As a result, the base is not a catalyst but is actually consumed as the reaction proceeds. After the reaction is complete, it is necessary to use a mild acid in order to protonate the doubly stabilized enolate. 

The biological decarboxylation of a P-keto acid presents a slight difficulty. We recall that carboxyhc acids exist as carboxylate anions at pH 7. And, the decarboxylation of P-keto acids occurs from the carboxylic acid, not the anion. Why, then, is this decarboxylation a favorable process Decarboxylation of oxalosuccinate produces an enolate anion. An enolate anion has a piST of -20 and is very unstable at pH 7. A reaction that produces an unstable intermediate has a high activation energy and is slow. Thus, the enzyme-catalyzed decarboxylation of the anionic form of a P-keto acid has to stabilize the enolate anion intermediate. Isocitrate dehydrogenase requires Mg ions. An Mg ion forms a complex with the carbonyl group of the P-keto acid. This has two effects. 

---