Insight into the Folding and Cooperative Multi‐Recognition Mechanism in Supramolecular Anion‐Binding Catalysis

H‐bond donor catalysts able to modulate the reactivity of ionic substrates for asymmetric reactions have gained great attention in the past years, leading to the development of cooperative multidentate H‐bonding supramolecular structures. However, there is still a lack of understanding of the forces driving the ion recognition and catalytic performance of these systems. Herein, insight into the cooperativity nature, anion binding strength, and folding mechanism of a model chiral triazole catalyst is presented. Our combined experimental and computational study revealed that multi‐interaction catalysts exhibiting weak binding energies (≈3–4 kcal mol(−1)) can effectively recognize ionic substrates and induce chirality, while strong dependencies on the temperature and solvent were quantified. These results are key for the future design of catalysts with optimal anion binding strength and catalytic activity in target reactions.