1. Aldehydes and ketones exist in equilibrium with enol tautomers:

The equilibrium is catalyzed by acid; that is, the rate at which equilibrium is reached is increased, but the position of the equilibrium is unaffected.

Base catalyzes the equilibrium as well; it also converts the enol to its conjugate base:

2. Other molecules having anion stabilizing groups also can be converted to enolates or equivalent structures by base:

All of these enolates have very similar structures, as can be seen by drawing resonsnce contributors or by examining the appropriate molecular orbitals.

3. Superbases

can convert all of these species irreversibly to enolates (conjugate bases).

4. If two stabilizing groups are present, alkoxide (RO^-) or hydroxide are strong enough bases to create high concentrations of enolate. The two most important "two-group" species are:

5. Enols and enolates undergo a variety of useful reactions:

• Halogenation (enol)

  

  This is an electrophilic attack by bromine on the enol double bond.

• Selenenylation (enolate)

  

  This reaction can be viewed as an electrophilic attack on the enolate, or as an S_N2 attack by the enolate on selenium.

  Selenenylation is useful because the phenyl selenide readily undergoes intramolecular elimanation to yield the conjugated enone.

  

• Malonic ester synthesis (enolate)

  

  The first step of this reaction is simply an S_N2 by the enolate on the alkyl halide.

  This reaction provides a ready synthesis of mono- and disubstituted acetic acids. The red box picks out a retrosynthetic key.

• Acetoacetic ester synthesis (enolate)

  

  Mechanistically identical to the malonic ester reaction (the first step again is an S_N2 reaction), this procedure gives substituted acetones. Again, the red box is the retrosynthetic key.

• Simple alkylation (enolate)

  Molecules containing only a single anion stabilizing group can be alkylated by use of superbases:

  

  These also are S_N2 reactions.

• Enamines, which are isoelectronic with enolates, can likewise be used as nucleophiles in an S_N2 process:

  

• In the aldol condensation, the reaction follows the standard nucleophilic addition mechanism from Chapater 19; the nucleophile adds to the carbonyl and a molecule of water is lost.

  

  In this example, we avoided self-condensation of the acetone by adding it to a mixture of the base with the benzaldehyde, which has no a-hydrogens. Alternatively, we could have reacted the acetone with LDA and added the aldehyde.

• Intramolecular aldols are facile when a 5- or 6-membered ring can be formed.

  

• In the first example, the enolate is that from malonic ester:

  

  Acetoacetic ester would behave identically.

• Double bonds conjugated to other anion stabilizing groups also undergo this reaction:

  

• Enolates stabilized by such groups also can act as nucleophiles:

  

9. Enolates also may behave as nucleophiles in nucleophilic acyl substitution reactions (Chapter 21). These processes are called Claisen condensations.

• In this example, we carry out a "crossed" Claisen in a similar manner to a crossed aldol, using one component having no a-hydrogens:

  

• An intramolecular Claisen is called a Dieckmann condensation, and can be used to construct 5- or 6-rings:

  

• As enolate equivalents, enamines can be used as the nucleophilic component in a Claisen-like reaction: