Stereoselectivity and expanded substrate scope of an engineered PLP-dependent aldolase

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.

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.

This lesson deals with the crossed aldol reaction using weak bases. The self-condensation of an aldehyde having α hydrogen is prevented by adding it slowly to a mixture of formaldehyde and weak bases like hydroxide and alkoxide. Upon slow addition of the aldehyde, the base deprotonates the α carbon of the aldehyde to form the corresponding enolate. The enolate subsequently attacks the formaldehyde to form a single crossed product. Figure 1 depicts the aforementioned reaction.

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.

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.

Crossed aldol addition is the reaction between two different carbonyl compounds under acidic or basic conditions. Here, both the carbonyl compounds function as nucleophiles and electrophiles. As shown in Figure 1, such a reaction yields a mixture of products, two of which are formed via self-condensation, while the remaining two are formed via crossed-condensation. Without adjustment, the reaction's usefulness in organic chemistry is decreased.