Probing the Synergistic Catalytic Model: A Rationally Designed Urea-Tagged Proline Catalyst for the Direct Asymmetric Aldol Reaction

A urea tag was incorporated at the C-4 position of proline, <i>cis</i> to its COOH group, in order to explore the prospect of a synergistic effect between the two functional groups in the transition state of the enamine route to the asymmetric aldol reaction. The catalyst proved to be an excellent performer, delivering aldols in high yields and with excellent enantio- and diastereoselectivities using just 2 mol % loading in the presence of water; it also exhibited good levels of recyclability under aqueous conditions. The favorable results reveal the interesting possibility of an intramolecular host–guest interaction between the urea and the amino acid moieties, exerting a beneficial effect on catalysis. The concept could certainly offer a new direction toward more efficient catalyst design