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 on either side of the other carbonyl. This is shown in figure 1, where the enolate derived from carbon 1 is equivalent to 6, and carbon 3 is equivalent to 4, thereby resulting in two possible distinct intramolecular nucleophilic attacks.

Figure 1. Possible enolates of a symmetrical diketone

As depicted in Figure 2, there are two possible intramolecular nucleophilic attacks. The attack on the carbonyl carbon 5 by the enolate formed at carbon 1 yields a stable five-membered ring. In contrast, the attack on the carbonyl carbon 2 by the enolate formed at carbon 4 generates a three-membered ring. As the three-membered ring is strained, the former intramolecular attack predominates to form a cyclic five-membered aldol product, which then dehydrates to yield the unsaturated cyclic product.

Figure 2. Two possible intramolecular nucleophilic attacks in a diketone molecule

In ketoaldehydes that possess an aldehyde group at one end and a ketone group at the other end, the positive inductive effect of the alkyl groups makes the ketone group less electropositive than the aldehyde. Hence, as shown in Figure 3, the enolates formed beside the ketone carbonyl group attack the aldehyde carbonyl group to form the stable six-membered cyclic product.

Figure 3. The intramolecular attack in a ketoaldehyde molecule