Enhanced cooperativity leading to high catalytic activity and stereoselectivity in the direct aldol reaction has been achieved through a complex network of simple species interacting reversibly.

A bifunctional organocatalytic system consisting of simple pyridine ligands containing separate catalytic functionalities was assembled using ZnCl2. This novel metal-templated catalyst furnished high yields and stereoselectivities towards the aldol reaction. The addition of controlled amounts of water turned out to be crucial to dissolve the system and achieve optimal results.

The study of novel metal-templated dynamic organocatalytic systems has led to the identification of CuSO as the most efficient template to assemble monofunctional prolinamide- and thiourea-modified pyridine ligands. The structural and electronic requirements to assemble an efficient catalyst have been disclosed: both pyridine ligands must bear a 1,3-substitution pattern, and the thiourea ligand serves as a reducing agent to copper(i) as well. Eventually, the cooperative effects achieved with such a simple system deliver high reaction rates and stereoselectivities at room temperature in the asymmetric aldol reaction, requiring only 1 mol% of copper salt.

A novel zinc‐templated complex, assembled from ZnCl2, picolinamide, and an unsymmetrical thiourea, efficiently catalyzes the asymmetric aldol reaction of ketones with aromatic aldehydes in wet THF as the solvent.