5.4: Reactivity of Enolate Ions

How Enolates React

Due to their negative charges, enolates are better and more versatile nucleophiles than enols. The increased reactivity of enolates makes them capable of a wider range of reactions than enols. Also, α-hydrogen containing compounds can be completely converted to an enolate by reaction with a strong base. Whereas enols can only be created in small amounts through manipulating their equilibrium.

Since the negative charge of an enolate anion is delocalized between the α-carbon and an oxygen, electrophiles may bond to either atom. Reactants having two or more reactive sites are called ambident, so this term applies to enolate anions. Either the C of the O reactive site in an enolate may act as a nucleophile depending on the reaction conditions. Reactions with the oxygen would create a new O-E bond and produce an enol derivative. Reactions with the α-carbon creates a new C-E bond and creates an α-substituted carbonyl compound. Although reactions with the nucleophilic oxygen are possible, reactions involving the nucleophilic α-carbon are much more common, partially due to the thermodynamic stability of the C=O bonds in the final products. Also, the enolate counter ion, such as Li⁺ or Na⁺, is more tightly associated with the negatively charged enolate oxygen which can then block incoming electrophiles, reducing their chance of reaction at the oxygen.

Stereochemical Implication of Enolate Formation

During enolate formation, an α-hydrogen is removed to form a sp²-hybridized, trigonal planar C=C bond which removes any chiral information from the original α-carbon. Because the enol alkene is planar, the incoming electrophile can attack from either the top or the bottom. If the α-carbon of the starting material has a defined stereochemistry or if a new stereocenter is formed during the reaction, the product will be a racemic mixture of enantiomers.

Base Promoted α-Halogenation

An enolate reacts rapidly with a halogen to produce α-halogenated carbonyl products. This reaction has the tendency to overreact and create polyhalogenated products. If a monohalogenated product is sought, the acid catalyzed halogenation reaction discussed previously is preferred. Because complete formation to the enolate is not necessary, weak bases, such as the hydroxide anion, are sufficient to produce this reaction. Once a small amount of enolate is formed, it quickly reacts with the halogen. This removes the enolate and shifts the equilibrium toward forming more enolate by Le Chatelier's principle.

Overreaction During Base Promoted α-Halogenation

The α-hydrogens of halogenated carbonyl products are usually more acidic than the corresponding non-halogenated compounds. The inductive electron withdrawing effect of the electronegative halogen stabilizes the negative charge of the enolate ion. This promotes further enolate formation and also further halogenation of the α-carbon. Monohalogenated carbonyls form an enolate over 100 times faster than their non-halogenated counterparts making multiple halogenations of the α-carbon frequent. This effect is exploited to cause the haloform reaction.