Aldol Reaction

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. Figure 1. Directed aldol reaction Let us consider the reaction between an aldehyde and a ketone in the presence of aqueous sodium hydroxide. As the aldehyde and ketone comprise α hydrogen, the reaction yields a mixture of...

Intramolecular aldol reaction occurs in dicarbonyl compounds such as dialdehydes, diketones, and keto-aldehydes. The dicarbonyl compounds possess more than one nucleophilic ⍺ carbon for the base to deprotonate and form the enolates. For example, in symmetrical diketones, there are four ⍺ carbons. Hence, four types of enolates are possible when treated with a base. However, since the molecule is symmetrical, the enolates formed on either side of one carbonyl group are equivalent to those formed...

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. Figure 1. Crossed aldol addition reaction of two...

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. Figure 1. The acid-catalyzed aldol addition reaction of ketones. First, as shown in Figure 2, the acid protonates the ketone molecule to form the protonated ketone. The conjugate base of the acid deprotonates the α carbon of the protonated ketone to form the enol. Figure 2. Formation of the enol.

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. Figure 1: The base-catalyzed aldol addition reaction of aldehydes. The reaction preferentially occurs with simple aldehydes, where the α carbon is monosubstituted. The equilibrium of the reaction involving disubstituted aldehydes and ketones shifts backward to the reactants due to the steric interactions at the α carbon. The...