Molecular Understanding and Practical In Silico Catalyst Design in Computational Organocatalysis and Phase Transfer Catalysis—Challenges and Opportunities

Abstract

Through the lens of organocatalysis and phase transfer catalysis, we will examine the key components to calculate or predict catalysis-performance metrics, such as turnover frequency and measurement of stereoselectivity, via computational chemistry. The state-of-the-art tools available to calculate potential energy and, consequently, free energy, together with their caveats, will be discussed via examples from the literature. Through various examples from organocatalysis and phase transfer catalysis, we will highlight the challenges related to the mechanism, transition state theory, and solvation involved in translating calculated barriers to the turnover frequency or a metric of stereoselectivity. Examples in the literature that validated their theoretical models will be showcased. Lastly, the relevance and opportunity afforded by machine learning will be discussed.

Theoretical Insight on the Formation Mechanism of a Trisubstituted Derivative of Closo-Decaborate Anion [B10H7O2CCH3(NCCH3)]0

“…The geometries of all model structures were fully optimised using the ωB97X-D3 functional in combination with the def2-TZVPP basis sets [38][39][40][41]. This method is applicable for a wide range of quantum chemical issues: atomic charges and chemical reactivity of organic and inorganic systems [42][43][44][45][46][47]. Previously, we have successfully applied the ωB97X-D3 functional for various calculations of closo-borate peculiarities: B-X (X = C, O, N, F) chemical bonding, non-covalent interactions, and molecular reactivity [35,48].…”

Mechanism of the Visible-Light-Promoted C(sp3)–H Oxidation via Uranyl Photocatalysis

“…Quantum computational chemistry plays an important role in the mechanism research today and provides numerous constructive suggestions including the confirmation of target structures, methodology development, and catalyst design. − Density functional theory (DFT) is a well-established and popular first-principle method in quantum chemistry, which has been extensively employed to investigate the mechanism of organic synthesis reactions, especially metal-catalyzed reactions. DFT calculations have been demonstrated to be reliable in revealing detailed potential energy surfaces and the geometric and electronic properties of reactants, products, intermediates, and transition states in various catalytic reactions. − In contrast to that of transition metals (e.g., Ru­(bpy) 3 2+ (bpy = 2,2′-bipyridine), − [Rh III (dtbbpy) 2 (I) 2 ] + (dtbbpy = 4,4′-di tert -butyl-2,2′-bipyridine) , ) involved in photocatalytic reactions, the theoretical study on the mechanism of the uranyl photocatalytic reaction is rare, especially for the important oxidation reaction of alkylbenzenes, ,, for which the oxidation products are pivotal for the production of many industrial products such as petrochemicals, pharmaceuticals, fragrance compounds, agrochemicals, etc.…”