Knoevenagel reaction amino acid catalysis

Ramachary and Reddy developed one of these sequences using an amino acid-catalyzed three-component reductive alkylation (TCRA) as the first reaction of their MCC. This multicomponent reaction involved an aldehyde 21, a malonate 22, and the Hantzsch ester 24 under amino acid catalysis starting with a Knoevenagel condensation, which was followed by hydrogenation of the formed olefin 23 to form... 

I2/K2C03, tetrabutylammonium hydroxide, tungsten phosphoric acid, ionic liquids, reactions in water, solvent-free conditions, microwave promoted reactions, reactions promoted by phase-transfer catalysts, and finally, for some very reactive substrates, uncatalyzed reactions. " Unfortunately for the practicing chemist, few of these conditions are well worked out enough or understood well enough to have become common, and almost all examples of the Knoevenagel condensation in the literature employ an amine base, or a salt thereof (Cope conditions, or amino acid catalysis) or TiCl4/Base(Lehnert conditions). ... 

The roots of iminium activation can be traced back to the pioneering works of Knoevenagel [4]. The Knoevenagel condensation became the first reaction that might proceed via iminium catalysis. Next, Pollack reported that several proteins and amino acids catalyzed the decarboxylation of acetoacetic acid. The mechanism suggested by Petersen involves an imine intermediate [5]. 

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