15.26: Aldol Condensation with β-Diesters: Knoevenagel Condensation
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
The reaction is catalyzed by amine base, which abstracts the acidic α hydrogen of the activated methylene to generate a resonance stabilized enolate ion. The basic strength of the amine is insufficient to form the enolate of aldehydes or ketones. However, it acts as a nucleophile that attacks the carbonyl compound to form an iminium ion intermediate. The nucleophilic enolate attacks the iminium ion to generate an addition product. Further protonation of the amino group in the adduct makes it a better leaving group. The base abstracts a second proton from the resulting molecule. It leads to a rearrangement step yielding the substituted olefinic product, thereby regenerating the amine catalyst.
