Self-assisted tandem Michael-aldol reactions of alpha,beta-unsaturated ketones with aldehydes

The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.

The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.

As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy carbonyl compound.

Benzaldehyde, like formaldehyde, lacks an α hydrogen and cannot enolize to form an enolate. Hence, the reaction of benzaldehyde with a ketone in the presence of an aqueous base forms a single crossed product. This reaction is referred to as Claisen–Schmidt condensation.
As the self-condensation of ketones is generally not favored in basic conditions, the self-condensed products do not form in the reaction between ketones and benzaldehyde. The general reaction of Claisen–Schmidt condensation is...

The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.

The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.