Aldol reactions

However if an Aldol addition is desired, this can usually be avoided with mild reagents and low temperatures (e.g., LDA (a strong base), THF, −78 °C).

[3] This is the basis of the catalytic strategy of class I aldolases in nature, as well as numerous small-molecule amine catalysts.

[4] If the catalyst is a moderate base such as hydroxide ion or an alkoxide, the aldol reaction occurs via nucleophilic attack by the resonance-stabilized enolate on the carbonyl group of another molecule.

When an acid catalyst is used, the initial step in the reaction mechanism involves acid-catalyzed tautomerization of the carbonyl compound to the enol.

The enol is nucleophilic at the α-carbon, allowing it to attack the protonated carbonyl compound, leading to the aldol after deprotonation.

This reaction is an important approach to the formation of carbon-carbon bonds in organic molecules containing ring systems.

Then, usually under heating conditions, the elimination of water molecule yields the cyclized α,β-unsaturated ketone, the aldol condensation product.

An example is the application of an intramolecular aldol reaction in the ring closure step for total synthesis of (+)-Wortmannin by Shigehisa, et al.[5] (Figure 2).