New Insights and Predictions into Complex Homogeneous Reactions Enabled by Computational Chemistry in Synergy with Experiments: Isotopes and Mechanisms

Abstract

Conspectus Homogeneous catalysis and biocatalysis have been widely applied in synthetic, medicinal, and energy chemistry as well as synthetic biology. Driven by developments of new computational chemistry methods and better computer hardware, computational chemistry has become an essentially indispensable mechanistic “instrument” to help understand structures and decipher reaction mechanisms in catalysis. In addition, synergy between computational and experimental chemistry deepens our mechanistic understanding, which further promotes the rational design of new catalysts. In this Account, we summarize new or deeper mechanistic insights (including isotope, dispersion, and dynamical effects) into several complex homogeneous reactions from our systematic computational studies along with subsequent experimental studies by different groups. Apart from uncovering new mechanisms in some reactions, a few computational predictions (such as excited-state heavy-atom tunneling, steric-controlled enantioswitching, and a new geminal addition mechanism) based on our mechanistic insights were further verified by ensuing experiments. The Zimmerman group developed a photoinduced triplet di-π-methane rearrangement to form cyclopropane derivatives. Recently, our computational study predicted the first excited-state heavy-atom (carbon) quantum tunneling in one triplet di-π-methane rearrangement, in which the reaction rates and 12C/13C kinetic isotope effects (KIEs) can be enhanced by quantum tunneling at low temperatures. This unprecedented excited-state heavy-atom tunneling in a photoinduced reaction has recently been verified by an experimental 12C/13C KIE study by the Singleton group. Such combined computational and experimental studies should open up opportunities to discover more rare excited-state heavy-atom tunneling in other photoinduced reactions. In addition, we found unexpectedly large secondary KIE values in the five-coordinate Fe­(III)-catalyzed hetero-Diels–Alder pathway, even with substantial C–C bond formation, due to the non-negligible equilibrium isotope effect (EIE) derived from altered metal coordination. Therefore, these KIE values cannot reliably reflect transition-state structures for the five-coordinate metal pathway. Furthermore, our density functional theory (DFT) quasi-classical molecular dynamics (MD) simulations demonstrated that the coordination mode and/or spin state of the iron metal as well as an electric field can affect the dynamics of this reaction (e.g., the dynamically stepwise process, the entrance/exit reaction channels). Moreover, we unveiled a new reaction mechanism to account for the uncommon Ru­(II)-catalyzed geminal-addition semihydrogenation and hydroboration of silyl alkynes. Our proposed key gem-Ru­(II)–carbene intermediates derived from double migrations on the same alkyne carbon were verified by crossover experiments. Additionally, our DFT MD simulations suggested that the first hydrogen migration transition-state structures may directly and quickly form the key gem-Ru–carbene structu...

Predicting Small Molecule Activation including Catalytic Hydrogenation of Dinitrogen Promoted by a Dual Lewis Acid

“…In recent years, computational chemistry has made significant contributions not only to the rationalization of experimental observations but also to the prediction of interesting structures and reactions. [67][68][69] Here, we demonstrate for the first time [4 + 2] cycloaddition reactions of a DLA with dinitrogen via theoretical predictions. It should be considered as a proof-ofconcept study as such a model molecule (DLA 1) has not been synthesized experimentally.…”

ReNeGate: A Reaction Network Graph-Theoretical Tool for Automated Mechanistic Studies in Computational Homogeneous Catalysis

“…The interactions between these components and their interconversions form large and highly interconnected reaction networks that determine the overall behavior and the performance of the catalytic system. The experimental and computational mechanistic studies aim at identifying the state of the catalytic species and key reaction intermediates, their role in the main catalytic mechanism, and the competing reaction channels toward unselective conversion routes or catalyst deactivation. − Such mechanistic insights are critically important for guiding the design and optimization of new and improved catalytic systems in a rational manner. − …”

“…The experimental and computational mechanistic studies aim at identifying the state of the catalytic species and key reaction intermediates, their role in the main catalytic mechanism, and the competing reaction channels toward unselective conversion routes or catalyst deactivation. 6 − 13 Such mechanistic insights are critically important for guiding the design and optimization of new and improved catalytic systems in a rational manner. 14 − 18 …”

ReNeGate: Reaction Network Graph Theoretical tool for automated mechanistic studies in computational homogeneous catalysis

“…The experimental and computational mechanistic studies aim at identifying the state of the catalytic species and key reaction intermediates, their role in the main catalytic mechanism and the competing reaction channels towards unselective conversion routes or catalyst deactivation. [6][7][8][9][10][11][12][13] Such mechanistic insights are critically important for guiding the design and optimization of new and improved catalytic systems in a rational manner. [14][15][16][17][18] Catalytic reactivity is determined by complex networks of chemical transformations that take place simultaneously or consequently between the different (transient) components of the catalytic mixture.…”