Stability of enolates

STABILIZATION OF ENOLATE ANIONS THE ENOLASE SUPER FAMILY... 

Stabilization of Enolate Anions The Enolase Super Family.173... 

A. C. Amyes, T. L. Formation and stability of enolates of acetamide and acetate anion an Eigen plot for proton transfer at y-carbonyl carbon./. Am. Chem. Soc. 2002, 124, 2957— 2968. 

Stabilization of enolate anions generated from abstraction of a proton a to a carboxylate Hydrolysis, phosphoryl group transfer via hydrolytic nucleophilic substitution Stabilization of diverse oxyanion intermediates via metal-assisted catalysis Schiff base dependent formation of an electron sink ... 

For compounds [53]—[55] the regioselectivity ratios for a and af H-D exchange have been interpreted in terms of the relative stabilities of enols [56]... 

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... 

The kinetically controlled nucleophilic addition of preformed lithium enolates onto carbonyl compounds is reversible with a low activation barrier, and the thermal conditions are likely to have a major impact on the stereoisomeric ratio of the final aldols through the retroaldolization and the thermodynamic equilibration of lithium enolates76. The tendency of aldolates to undergo retroaldolization increases with the stability of enolates, and when going from lithium to potassium. On the other hand, boron enolates usually undergo completely irreversible aldol reaction511,512. 

Like the H-bonding in the above examples, metal ions also serve as general acids and are involved in stabilization of enolate intermediates in many biological processes which are discussed in the following sections. 

Other examples of electrophilic substitution reactions catalyzed by metal ions through mechanisms involving the promotion of proton loss and stabilization of enol forms of reactants include the bromination of /3-diketones ... 

So, the substance of the Gerlt-Gassman/Cleland-Kreevoy proposals appears correct, i.e., hydrogen bonding can provide much more stabilization of enolate anion intermediates under conditions of appropriate local dielectric environment than had been previously recognized by the bioorganic and biochemical communities. 

A useful application of an enolate-oxime ether condensation, described by Weeks, Volkmann and co-woricers, is found in the synthesis of 6-aminomethylpenicillin derivative (218), a potent -lactamase inhibitor. As shown in Scheme 45, the sensitive penicillin Grignard (216) is condensed with ethyl formaldoxime at -80 C in the presence of Bp3-OEt2 to afford adduct (217). The use of Bp3-OEt2 is critical because it allows the reaction to proceed at the low temperature required for the stability of enolate (216). Hydrogenolysis of (217) simultaneously results in removal of the ethoxy, bromo and benzyl groups, affording (218). 

By comparison, decarboxylation is largely a kinetic problem. Enzymes have developed a variety of strategies for stabilizing the anionic intermediate that is produced in the decarboxylation step. Metal ion stabilization of enolates is a common theme, particularly for decarboxylation of /8-keto acids. The most elegant solutions are perhaps the extensive electron delocalizations seen in pyri-doxal phosphate and thiamin pyrophosphate. 

Thinking about the stability of enols bearing stabilizing substituents. 

The base produces an anion at the a position of the imine. This cm banion is stabilized by conjugation with the cm bon-nitrogen double bond, in a mode closely resembling the stabilization of enolates. 

The surprising stability of enolate 39 towards P-elimination of the axial glycosidic OCH3 is obviously related to its carbohydrate nature, since such an axial substituent on a carbocyclic ring would not have been expected to survive. 

Under these conditions, the more stable enolate anion predominates. The factors that determine the relative stabilities of enolate anions are the same as those that determine the relative stabilities of alkenes the more substituted the double bond of the enolate anion, the greater its stability. Thus, the composition of the enolate anion mbcture formed under conditions of thermodynamic control reflects the relative stabilities of the individual enolate anions. 

FIGURE 19.22 The formation of an intramolecular hydrogen bond, as well as conjugation between the carbon-carbon double bond and the carbonyl group, contributes to the increased stability of enols in P-dicarbonyl compounds. 

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