Enols, Enolates and Aldol Condensation | Organic Chemistry 2

The enols, enolates and aldol condensation are studied in this chapter: the acidity of carbonyls, the keto-enol equilibria, the alkylation of carbonyls, the aldol and cross-aldol condensation, the unsaturated aldehydes and ketones (1,2- and 1,4-additions).

Acidity of Carbonyls

H on an α-carbon of a carbonyl is acidic ⇒ pKa ~ 16-18 (aldehyde) and ~ 19-21 (ketone).

 

 

Base has to be strong (pKa > 21) ⇒ LDA, KH, KOtBu, BuLi

Keto-Enol Equilibria

Carbonyls are in equilibrium with their enol forms (10 kcal.mol-1 less stable):

 

Mechanisms:

Base-Catalyzed Enol-Keto Equilibration:
 

 

Acid-Catalyzed Enol-Keto Equilibration:
 

Alkylation of Carbonyls


Mechanism:
R-X must be primary halide (SN2 reaction).

 

 

 


Mechanism:
R-X must be primary or secondary halide (SN2 reaction).


 

Synthetic Strategy: 
Advantage of Enamine Alkylation:
- No polyalkylation ( = Enolate Alkylation)
- More reactive: R-X can be a secondary halide

Aldol Condensation


Mechanism:

Step 1: Enolate Generation
 


Step 2: Nucleophilic attack followed by a Protonation
 


Step 3: Aldol Dehydration
 

 

Aldol Condensation of ketones is possible but the step 1 is energically unfavorable (ketones are more stable than aldehydes).
To drive the equilibrium ⇒ removal of the water (or the aldol) formed.

Intramolecular aldol condensation succeeds with both aldehydes and ketones.
It gives the least strained cycloalkenones (highly regioselective).

Cross Aldol Condensation


Product mixtures unless one of the reaction partners cannot enolize

α,β-Unsaturated Aldehydes and Ketones

Stability: Stabilized by resonance

Reactivities:
- reactions typical of alkenes and carbonyls
- 1,4-additions (and sometimes 1,2-additions)

 

1,4-additions:
 

with Nu = Nucleophile; E = Electrophile (generally H+)