The Cation–π Interaction in Small‐Molecule Catalysis

Abstract

Catalysis by small molecules (≤ 1000 Da, 10−9 m) capable of binding and activating substrates via attractive, noncovalent interactions has emerged as an important approach in organic and organometallic chemistry. While the canonical noncovalent interactions—including hydrogen-bonding, ion-pairing, and π-stacking—have become mainstays of catalyst design, the cation–π interaction has been comparatively underutilized in this context since its discovery in the 1980s. However, like a hydrogen bond, the cation–π interaction exhibits a typical binding affinity of several kcal/mol with substantial directionality. These properties render it attractive as a design element for the development of small-molecule catalysts, and in recent years, the catalysis community has begun to take advantage of these features, drawing inspiration from pioneering research in molecular recognition and structural biology. This review surveys the burgeoning application of the cation–π interaction in catalysis.

Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

“…These data show that the bulk of this enhancement is due to electrostatic effects . In other words, the electrostatically driven π⋅⋅⋅π + interaction in Y′ controls the conformation of the activated catalyst, overriding the intrinsic conformational preference for X / X′ …”

Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction

“…16 Asymmetric induction is typically achieved from the resultant ion pair as a consequence of specific attractive non-covalent interactions between the corresponding cationic intermediate and the chiral HBD catalyst. 17,18,19 Reported examples have been limited to heteroatom-stabilized cations, due to the challenges in generating the requisite ion pair and suppressing elimination/rearrangement pathways. The ability of HBD catalysts to control enantioselective nucleophile addition into non-heteroatom stabilized carbocations has to our knowledge not been demonstrated.…”

Catalysis with Pnictogen, Chalcogen, and Halogen Bonds

“…[1][2][3][4] It enables the creation of novel, unprecedented architectures and holds promise to access new properties.W ell-known interactions such as dispersion forces, [3] ion pairing, [4] hydrogen bonding, [5] and cation-p interactions [6] play ak ey role in the function of organocatalysts.I na ne ffort to expand the interaction toolbox available to chemists,l esser known interactions such as anion-p interactions,t he unorthodox counterpart of cation-p interactions,h ave been introduced recently to organocatalysis. [7] Another family of unorthodox interactions are the so called s-hole interactions ( Figure 1).…”