A Computational Approach to Interpret Selectivity and Reactivity in Organo-, Supramolecular, Electrochemical and Photo-redox Catalysis

Efficient and selective catalysis is predominant in chemistry, enabling the synthesis of molecules and materials with enormous societal and technological impact. Computational chemistry provides a versatile toolbox for studying mechanistic details of catalytic reactions and holds promise to deliver practical strategies to enable the rational in silico catalyst design. Diversity in reactivity, nontrivial electronic structure effects, solvation effects and impact of non-covalent weak dispersive interactions introduce additional complexity that represents a pressing challenge to the conventional synthetic methodologies. Modern in silico tools such as the density functional theory (DFT) and other sophisticated physical techniques assess the energetic landscape quite accurately and provide critical insights on conformational flexibility in predicting stereo-, regio and chemo-selectivity. Herein, we aim to discuss the factors such as non-covalent interactions (NCIs), steric or confinement effects that leads to fascinating transformations through organo-, supramolecular, electrochemical and photo-redox catalysis. In a recent study we predicted the unique role of indole molecules which stabilizes the transition states during the dehydrogenation process of polyfluorinated alcohols, through non-covalent π-π and H-bonding interactions. This study put forth a straightforward protocol to develop biologically relevant fluoroalkyl bis-indoles in a sustainable fashion through in-depth insights gained from extensive DFT predictions. Furthermore, our recent study unfurls the crucial role of NCIs in electrochemical synthesis of unsymmetrically substituted NH-pyrroles from enamines. Trifluoroethanol additives are found to have “magical effect” on tuning oxidation potential of enamines through H-bonding and C-H···π interactions, thus facilitating the desired chemo-selective cross-coupling. Further, we discuss how combined effect of NCIs and removal of steric encumbrance underpin chirality in bifunctional squaramide catalysed reactions leading to skeletal diversity in synthesis of azocine derivatives. Additionally, we also discuss how an electron donor acceptor (EDA) complex promotes visible light mediated (4 + 2) radical annulation between alkyl NHPI esters and N-substituted maleimides. Lastly, we show a supramolecular capsule arrangement of resorcin-arene that facilitates coupling of pyrrole and isocyanates in a solvent-free environment, simply backed by confinement effects.