Non‐covalent molecular interactions on the basis of halogen and chalcogen bonding represent a promising, powerful catalytic activation mode. However, these “unusual” non‐covalent interactions are typically employed in the solid state and scarcely exploited in catalysis. In recent years, an increased interest in halogen and chalcogen bonding has been awaken, as they provide profound characteristics that make them an appealing alternative to the well‐explored hydrogen bonding. Being particularly relevant in the binding of “soft” substrates, the similar strength to hydrogen bonding interactions and its higher directionality allows for solution‐phase applications with halogen and chalcogen bonding as the key interaction. In this mini‐review, the special features, state‐of‐the‐art and key examples of these so‐called σ‐hole interactions in the field of organocatalysis are presented.

Halogen bonding represents a powerful tool in the field of noncovalent interactions. However, applications in enantioselective recognition and catalysis remain almost nonexistent, due in part to the distinct features of halogen bonds, including long covalent and noncovalent bond distances and high directionality. Herein, this work presents a novel chiral tetrakis‐iodo‐triazole structure as a neutral halogen bond donor for both chiral anion‐recognition and enantioinduction in ion‐pair organocatalysis. NMR‐titration studies revealed significant differences in anion affinity between the halogen bonding receptor and its hydrogen bonding parent. Selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction were demonstrated using the halogen bond donor. Inversions in the absolute sense of chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor were observed. Computational modeling suggested that these effects were the result of distinct anion‐binding modes for the halogen‐ versus hydrogen‐bond donors.

H-bond donor catalysts able to modulate the reactivity of ionic substrates for asymmetric reactions have gained great attention in the past years, leadingt ot he development of cooperative multidentate H-bonding supramolecular structures. However,t here is still al ack 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 am odel chiral triazole catalysti sp resented. Our combinede xperimentala nd computational study revealedthat multi-interaction catalysts exhibiting weak binding energies (% 3-4 kcal mol À1)c an effectively recognize ionic substrates and induce chirality,w hile strong dependencies on the temperature and solventw ere quantified. These results are key for the future design of catalystsw ith optimal anion bindings trength and catalytica ctivity in target reactions.