15.5 : Regioselective Formation of Enolates

Recall that the α-hydrogen atoms of carbonyl compounds are weakly acidic. When deprotonated by a base, they generate resonance-stabilized enolate ions.

Unsymmetrical ketones bearing nonequivalent α-hydrogen atoms yield two possible intermediates–less substituted or more substituted enolates.

As deprotonation is easier for a less-hindered proton, less-substituted enolates are formed comparatively faster. These are known as kinetic enolates. Because the more-substituted enolates bear a highly substituted double bond, they are more stable, and often known as thermodynamic enolates. Thus, thermodynamic enolates are at lower energy levels than kinetic enolates.

As the energy required to form thermodynamic enolates is higher, its formation requires a longer reaction time.

Regioselective formation of the enolates is possible depending on the reaction conditions.

To generate kinetic enolates, bulky non-nucleophilic strong bases in aprotic solvents are used to specifically abstract unhindered protons. In addition, maintaining a low reaction temperature forbids the equilibration of the two enolates.

As opposed, nonsterically hindered bases in protic solvents at room temperature favors formation of the thermodynamic enolate.