15.21:
Crossed Aldol Reactions: Overview
A crossed aldol reaction is an aldol condensation reaction between two different carbonyl compounds, at least one of which has an α hydrogen atom, with one compound acting as the nucleophile and the other as the electrophile.
If both carbonyl compounds can enolize, this reaction yields a mixture of products: two formed via self-condensation, and two via crossed-condensation.
In this reaction, preventing self-condensation is key to reaction efficiency by minimizing the number of products formed.
For example, formaldehyde, with no α hydrogen atoms, behaves solely as an electrophile while reacting in a base with another aldehyde that does contain α hydrogen atoms to yield a single crossed aldol product.
Other popular reactions that exhibit a similar phenomenon are Claisen–Schmidt condensation, the directed aldol reaction, and the Reformatsky reaction.
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.