15.19 : 分子内アルドール反応

Dicarbonyl compounds like dialdehydes, diketones, and keto-aldehydes in the presence of an acid or base, undergo an intramolecular aldol reaction to yield stable five or six-membered cyclic products.

In diketones, the base can deprotonate four of the nucleophilic alpha-carbons to form the corresponding enolates.

In a symmetrical diketone, the enolates derived from carbons 1 and 6 are equivalent, as are those from carbons 3 and 4, resulting in two possible intramolecular attacks. 

The nucleophilic attack on carbonyl carbon 5 by carbon 1 and carbonyl carbon 2 by carbon 4 generates cyclic five-membered and three-membered aldol products, respectively. While the strained three-membered aldol product is not formed, the five-membered aldol product dehydrates to give cyclopentenone.

In keto-aldehydes, the two electron-donating alkyl groups connected to the carbonyl carbon make it less electropositive in ketones as compared to aldehydes. Hence, the carbonyl of aldehyde is more electrophilic and attacked by the ketone enolate to form the stable cyclic product.