Ambident enolate

The same behavior has been observed in the attack of electrophiles on the ambident enolate anions, of which many reactions are closely related to those of enamines [Eq. (2)] ... 

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

These results clearly show that the potential energy surface can contain a series of minima. The fact that selectivity in re-attack by the F ions can be observed indicates that the differences between the energy barriers for the secondary reactions control the distribution of the final products. The multistep character of these processes is further illustrated by the reactions observed when enolate anions are used as reactant ions. The ambident enolate anions may react with methyl pentafluorophenyl ether at the carbon or the oxygen site. If they react with the carbon site at the fluorine-bearing carbon atoms, then the molecule in the F ion/molecule complex formed contains relatively acidic hydrogen atoms so that proton transfer to the displaced F ion may occur. An example is given in (47) where the enolate anion, generated by HF loss, is not observed. An intramolecular nucleophilic aromatic substitution occurs instead and leads to a second F ion/ molecule complex. The F" ion in this complex then re-attacks the substituted benzofuran molecule formed, either by proton transfer or SN2 substitution. 

Second, and as discussed in Part A, Chapter 5, nucleophilicity in Sn2 reactions is associated with polarizability. The more easily a nucleophile s electronic cloud can be distorted to permit bond formation, the stronger an Sn2 nucleophile it will be. Comparison of the oxygen and carbon ends of an ambident enolate ion with regard to nucleophilicity leads to the conclusion that the less electronegative carbon atom is more polarizable and to the prediction that the carbon end of the anion will be more nucleophilic. 

The alkylation of ambident enolates of a methyl glycinate Schiff base has been studied computationally/ Although the E- and Z-enolates have similar energy and geometry, and similar transition states with ethyl chloride, the -enolate is substantially more stabilized by lithium cation. 

The influence of the coordination of lithium and sodium enolates on the stereochemical outcome of their aldol reactions has been reviewed. The alkylation of the ambident enolates of a methyl glycinate Schiff base with ethyl chloride have been studied at B3LYP and MP2 levels. The transition states for the alkylation of the free ( )/(Z)-enolate with ethyl chloride have energy barriers of 13kcalmol However, with a lithium ion, the ( )-enolate behaves as an ambident enolate and makes a cyclic lithium complex in bidentate pattern, which is more stable by 11-23 kcal mor than the (Z)-enolate-lithium complexes. The results suggest that the alkylation of ambident enolates proceeds with stable cyclic bidentate complexes in the presence of metal ion and solvent. 

The base-catalysed rearrangements of cz-halo ketones are classical examples of the reactions of ambident enolate anions in solution. The extent of each of the two reactions shown in Equations [11] and [12] is principally a function of the type of solvent used. A protic solvent solvates more strongly at the oxygen centre of the ambident anion and thus reaction proceeds through the carbanion centre to yield the Favorskii species as the major product (Eqn [11]). In marked contrast, the Favorskii rearrangement does not occur in the gas phase. Here,... 

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