Evaluation of 6-APA as a New Organocatalyst for a Direct Cross-Aldol Reaction

6-Aminopenicillanic acid (6-APA) and two of its derivatives, 6-APA benzyl ester (6-APA-OBn) and Penicillin G (PenG), have been evaluated as catalysts for use in direct cross-aldol reactions in different solvents and mixtures. The effects of catalyst loading, reaction time, pH and temperature on the yield and stereoselectivity have been studied, 6-APA proved to be an effective catalyst in terms of yield for the reaction between cyclohexanone and p-nitrobenzaldehyde, especially in neat conditions. The stereoselectivity of the reaction was conditioned by the presence of two competing mechanisms: one an imine-enamine pathway and the other a Bronsted acid catalysis. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)