Aldol-like Reactions

Many variations of aldol reaction were established. These work on the same principle as classical aldol reaction does, such as ...

• ... intramolecular aldol reaction, which yields cyclic compounds.
• ... crossed aldol reaction, in which two different carbonyl compounds are applied together, resulting in a variety of products.
• ... Knoevenagel reaction, in which particularly strongly CH-acidic compounds, such as 1,3-dicarbonyl compounds or nitroalkanes, are applied instead of a "simple" enolate.
• ... Michael reaction, in which the conjugated base (anion) of a CH-acidic compound is added to the β carbon of an α,β-unsaturated carbonyl compound. If the CH-acidic compound is an aldehyde or a ketone, the Michael reaction yields a 1,5-dicarbonyl compound.
• ... Robinson annulation, which is a combination of a Michael reaction and a subsequent intramolecular aldol condensation. Robinson annulation is useful for the construction of complex aliphatic ring skeletons, such as that of steroids and terpenes.

Knoevenagel condensation:InKnoevenagelcondensation, particularly strongly CH-acidic compounds, such as 1,3-dicarbonyl compounds or nitroalkanes, are applied instead of a "simple" enolate.

Knoevenagel Condensation

In a variation of the aldol reaction, other CH-acidic compounds are applied instead of the classical enol. Theoretically, every carbanion is capable of nucleophilically attacking the electrophilic carbonyl group of aldehydes and ketones.

KNOEVENAGEL CONDENSATION

The condensation of aldehydes or ketones with a variety of CH-acidic compounds in the presence of a base, such as a tertiary amine or KOH, is called Knoevenagel condensation.

The reaction is named after Emil Knoevenagel (1865-1921). In comparison to aldehydes and ketones (pKa values: 14-20), 1,3-diketones or β-keto carbonyl compounds are much stronger acids (pKa values: 5-13). Thus, they can relatively easily be deprotonated to the corresponding carbanion or enolate. Nitroalkanes, depicted in the second example in the illustration below, are considerably CH-acidic compounds (pKa values about 10). As a result, they may be successfully applied in the Knoevenagel condensation. This reaction is also often called the Henry reaction. Due to the relatively high acidity of the CH-acidic compounds applied in the Knoevenagel condensation, only a relatively weak base, such as an amine or KOH, is required. Much like in aldol reactions, the addition of the carbanion to the carbonyl compound is frequently followed by dehydration.