Harnessing Selectivity and Reactivity with Noncovalent Interactions in Molecular and Supramolecular Organo‐Catalysis: A Computational Perspective

Abstract Noncovalent interactions (NCIs), such as hydrogen bond, halogen bond, hydrophobic effect, π‐stacking, etc., have been integral to biocatalysis, and their application to chemical catalysis has been accelerated over the past two decades. Although the underpinning of these relatively complex interactions is still a challenging foray, advancement in density functional theory and high‐level calculations with wave‐function‐based quantum mechanical approaches have led to reliable interpretations of these weak interactions, with sufficient accuracy, to provide meaningful insights on their physical origins in molecular binding and chemical transformations. Such an in‐depth understanding of electronic structure and reactivity offers possibilities for judicious engineering of these complex intra/intermolecular interactions to achieve enzyme‐like optimum efficacy. In this study, we therefore focus on applications that demonstrate the advantages of rational manipulation of noncovalent interactions in molecular and supramolecular organocatalytic frameworks, pertaining to chiral catalysis, electron‐donor acceptor events in photo‐redox catalysis, or transformations within confined spaces of self‐assembled capsules and cages. We emphasize on how quantum chemical data analysis provides reasonable indications of catalyst performance. We also highlight the ongoing challenges in computing reaction outcomes and discuss remedial approaches. We believe this overview would provide guiding principles for the successful designing of organo‐catalysts using noncovalent weak interactions.