Enolates are important organic reactive intermediates. They have the dual characteristics of both alkoxide and carbanion.
Enolates can be synthesized from carbonyl compounds, such as aldehydes and ketones, by the protonation of the oxygen atom followed by deprotonation of the alpha-carbon atom. This can be done in the presence of an acid and base. These intermediates can then be used in a variety of reactions, including the aldol reaction and the Michael reaction.
These are used in organic synthesis and are often used in the preparation of complex molecules.
Preparation of Enolates
The enolizable ketone, aldehyde, alcohols, and esters generally form enolate ions. Typically enolates are synthesized by using LDA (lithium diisopropylamide).
Formation of regioselective Enolates
When there are two sites for the proton abstraction in the carbonyl compounds, then two different enolate products are formed.
For example, an unsymmetrical ketone such as 2-methyl cyclohexanone can form two possible enolates.
The stability of enolate can be predicted in the same way as for alkenes. Therefore, the more substituted enolate is more stable. However, sometimes the more substituted enolate is not a thermodynamic more stable enolate. This is because in some cases steric hindrance destabilizes the more substituted enolate.
Factor affecting the formation of Enolates
The synthesis of enolate is an acid-base reaction. The following factors can control the position of equilibrium:
- Solvent
- Base
- Cation
- Temperature
Factors favor the formation of the kinetic enolates
There are the following factors that favor the formation of kinetic enolates, such as aprotic solvents such as THF can be used to prepare kinetically stable enolates. Its formation can also be enhanced by strong bases such as LDA and oxophilic cations (Li+). Moreover, this reaction proceeds quite well at low temperatures i.e. -78°C.
Factors favor the formation of a thermodynamic enolates
To prepare the thermodynamically stable enolate, it is recommended to use protic solvents such as alcohol because the weak base can generate strong conjugate acid which increases the yield. however, this reaction is favored at high temperatures.
Reactions of Enolates
`Enolates are ambident nucleophiles. Therefore, they react with a variety of electrophiles.
Alkylation of enolate
Firstly LDA is used to generate the enolate ion (as discussed above). LDA has two isopropyl groups and a negative charge on nitrogen, making it a significantly hindered base. So, it can’t attack the carbonyl group to abstract the alpha hydrogen. Further, it is much more basic than sodium hydroxide, therefore we can use only one equivalent.
In the second step, alkyl halide is added to the enolate solution. The enolate attacks electropositive carbon next to the bromide. The final molecule is produced by extending the carbon chain by three carbon atoms. Note that, this reaction works best with primary alkyl halides because of no steric hindrance.
Related resources
- Diels Alder Reaction: Examples, Mechanism, and Stereochemistry
- Wittig Reaction, Example, Mechanism, and Stereochemistry.
Concepts Berg
What is enol?
Enols are the organic compound containing both alcohol and alkene functional groups. It’s name is the combination of alkenes suffix and -ol from alcohol.
What bases form enolates?
Weak bases like alcohol have the tendency to make enolates.
Can I stop the aldol reaction from happening after enolate forms?
This is possible if a strong base such as LDA is used.
Difference between enol and enolate?
Enols are alkenes with an alcohol group whereas enolate is a negatively charged reactive intermediate.
Is an enolate a nucleophile?
Yes, enolate is a strong nucleophile.
Is enolate an acid?
Enolate is the conjugate base. After the removal of weakly acidic alpha hydrogen, it is stabilized by the conjugation of pi electrons of the oxygen atom with carbonyl carbon.
References
- Chapter 18 (utexas.edu)
