15.21 : Crossed Aldol Reactions: Overview

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 different aldehydes

Various strategies are employed to prevent self-condensation and improve the reaction's efficiency. For example, if one of the two reacting carbonyl compounds has no α hydrogen, such as the formaldehyde, it cannot form the enolate ion in the presence of a base. Hence, the reaction of formaldehyde with another carbonyl compound that does have an α hydrogen yields a single crossed aldol product. Here, the formaldehyde functions exclusively as an electrophile. Claisen–Schmidt condensation, directed aldol reaction, and the Reformatsky reaction also aim to yield a single crossed aldol product.