In the last few decades, "unusual" noncovalent interactions like anion-π and halogen bonding have emerged as interesting alternatives to the ubiquitous hydrogen bonding in many research areas. This is also true, to a somewhat lesser extent, for chalcogen bonding, the noncovalent interaction involving Lewis acidic chalcogen centers. Herein, we aim to provide an overview on the use of chalcogen bonding in crystal engineering and in solution, with a focus on the recent developments concerning intermolecular chalcogen bonding in solution-phase applications. In the solid phase, chalcogen bonding has been used for the construction of nano-sized structures and the self-assembly of sophisticated self-complementary arrays. In solution, until very recently applications mostly focused on intramolecular interactions which stabilized the conformation of intermediates or reagents. In the last few years, intermolecular chalcogen bonding has increasingly also been exploited in solution, most notably in anion recognition and transport as well as in organic synthesis and organocatalysis.

Halogen bonding is a noncovalent interaction similar to hydrogen bonding, which is based on electrophilic halogen substituents. Hydrogen-bonding-based organocatalysis is a well-established strategy which has found numerous applications in recent years. In light of this, halogen bonding has recently been introduced as a key interaction for the design of activators or organocatalysts that is complementary to hydrogen bonding. This Concept features a discussion on the history and electronic origin of halogen bonding, summarizes all relevant examples of its application in organocatalysis, and provides an overview on the use of cationic or polyfluorinated halogen-bond donors in halide abstraction reactions or in the activation of neutral organic substrates.

Halogen bonding, the noncovalent interaction based on electrophilic halogen substituents, features very interesting properties, as illustrated by numerous applications continuously emerging in recent years, and is by now sometimes considered as a hydrophobic and soft analogue of the well-known hydrogen bond. Conventionally studied both in silico and in the solid state, its solution-phase applications particularly for catalyzing organic transformations are currently under active investigation. Herein we present a conceptual treatise on the latest developments in this regard and discuss the challenges associated with the advancement of more practical catalytic halogen-bonding systems.

I⋅⋅⋅Br‐idging: Benzhydryl bromide can be activated by novel halogen‐bond donors and subsequently undergoes a Ritter‐like reaction with acetonitrile (see scheme). Comparative experiments with non‐iodinated reference compounds and tests with added acids indicate that halogen bonds are very likely the basis for this effect. The activation seems to be applicable to other substrates as well.

In contrast to hydrogen bonding, which is firmly established in organocatalysis, there are still very few applications of halogen bonding in this field. Herein, we present the first catalytic application of cationic halogen-bond donors in a halide abstraction reaction. First, halopyridinium-, haloimidazolium-, and halo-1,2,3-triazolium-based catalysts were systematically tested. In contrast to the pyridinium compounds, both the imidazolium and the triazolium salts showed promising potency. For the haloimidazolium-based organocatalysts, we could show that the catalytic activity is based on halogen bonding using, e.g., the chlorinated derivatives as reference compounds. On the basis of these studies, halobenzimidazolium organocatalysts were then investigated. Monodentate compounds featured the same trends as the corresponding imidazolium analogues but showed a stronger catalytic activity. In order to prepare bidentate versions which are preorganized for anion binding, a new class of rigid bis(halobenzimidazolium) compounds was synthesized and structurally characterized. The corresponding syn isomer showed unprecedented catalytic potency and could be used in as low as 0.5 mol % in the benchmark reaction of 1-chloroisochroman with a silyl enol ether. Calculations confirmed that the syn isomer may bind in a bidentate fashion to chloride. The respective anti isomer is less active and binds halides in a monodentate fashion. Kinetic investigations confirmed that the syn isomer led to a 20-fold rate acceleration compared to a neutral tridentate halogen-bond donor. The strength of the preorganized halogen-bond donor seems to approach the limit under the reaction conditions, as decomposition is observed in the presence of chloride in the same solvent at higher temperatures. Calorimetric titrations of the syn isomer with bromide confirmed the strong halogen-bond donor strength of the former (K ≈ 4 × 10(6) M(-1), ΔG ≈ 38 kJ/mol).