Controlling the Redox Properties of Organic Catalysts and Organic Photocatalysts – CO2 Reduction by Renewable Organo-Hydrides and Photocatalyzed Polymerization using Visible Light

The efficient chemical reduction of CO2 to fuels has been of interest to scientists for decades with growing concerns about the impact of CO2 on climate and future global energy demands motivating increasing efforts to meet this challenge. One conversion of specific interest — the reduction of CO2 to methanol (CH3OH) — is the focus of my thesis. Arguments here involve CH3OH’s utility as a practical C1 source for chemical synthesis and its attractive properties as a fuel not demanding the massive changes to the transportation fuels infrastructure required for a hydrogen economy. My thesis focuses on understanding the role of pyridine in catalyzing the conversion of CO2 to CH3OH. In particular, I employed quantum chemical simulations as an invaluable tool to probe the redox properties of a number of pyridine-derived intermediates involved in the catalytic cycle of CO2 reduction. Accurate determination of redox properties, e.g. reduction potentials and hydricity is important to paint a detailed picture of energetics involved in the transformation of transient species during the course of CO2 reduction, and thus the role of the catalytic species is revealed. One central aspect is the determination of the driving force to effect hydride transfer. 1,2-dihydropyridine (PyH2) is a potent recyclable organo-hydride donor because it is driven by its proclivity to regain aromaticity; this mimics important aspects of the role of NADPH in the formation of C-H bonds in the photosynthetic CO2 reduction process. The aspect of controlling redox properties of molecules was applied to organic photocatalyst that affects photo-polymerization. In collaboration with the Stansbury’s group, we elucidated the mechanism of polymer synthesis involving methylene blue chromophore with a sacrificial sterically-hindered amine reductant and an onium salt oxidant. The combination of these components yield interesting results: light-initiated free-radical polymerization continues over extended time intervals (hours) in the dark after brief (seconds) low-intensity illumination. We proposed that these observations are due to the latent production of free radicals from energy stored in a redox potential through a 2e-/1H+ transfer process, which transforms the methylene blue chromophore to its high energy closed-shell intermediate of leuco methylene

Visible-Light-Promoted C–S Cross-Coupling via Intermolecular Charge Transfer

Disclosed is a mild, scalable, visible-light-promoted cross-coupling reaction between thiols and aryl halides for the construction of C–S bonds in the absence of both transition metal and photoredox catalysts. The scope of aryl halides and thiol partners includes over 60 examples and therefore provides an entry point into various aryl thioether building blocks of pharmaceutical interest. Furthermore, to demonstrate its utility, this C–S coupling protocol was applied in drug synthesis and late-stage modifications of active pharmaceutical ingredients. UV–vis spectroscopy and time-dependent density functional theory calculations suggest that visible-light-promoted intermolecular charge transfer within the thiolate–aryl halide electron donor–acceptor complex permits the reactivity in the absence of catalyst

Mechanism of Homogeneous Reduction of CO₂ by Pyridine: Proton Relay in Aqueous Solvent and Aromatic Stabilization

We employ quantum chemical calculations to investigate the mechanism of homogeneous CO₂ reduction by pyridine (Py) in the Py/p-GaP system. We find that CO₂ reduction by Py commences with PyCOOH⁰ formation where: (a) protonated Py (PyH⁺) is reduced to PyH⁰, (b) PyH⁰ then reduces CO₂ by one electron transfer (ET) via nucleophilic attack by its N lone pair on the C of CO₂, and finally (c) proton transfer (PT) from PyH⁰ to CO₂ produces PyCOOH⁰. The predicted enthalpic barrier for this proton-coupled ET (PCET) reaction is 45.7 kcal/mol for direct PT from PyH⁰ to CO₂. However, when PT is mediated by one to three water molecules acting as a proton relay, the barrier decreases to 29.5, 20.4, and 18.5 kcal/mol, respectively. The water proton relay reduces strain in the transition state (TS) and facilitates more complete ET. For PT mediated by a three water molecule proton relay, adding water molecules to explicitly solvate the core reaction system reduces the barrier to 13.6–16.5 kcal/mol, depending on the number and configuration of the solvating waters. This agrees with the experimentally determined barrier of 16.5 ± 2.4 kcal/mol. We calculate a p<i>K</i> _a for PyH⁰ of 31 indicating that PT preceding ET is highly unfavorable. Moreover, we demonstrate that ET precedes PT in PyCOOH⁰ formation, confirming PyH⁰’s p<i>K</i> _a as irrelevant for predicting PT from PyH⁰ to CO₂. Furthermore, we calculate adiabatic electron affinities in aqueous solvent for CO₂, Py, and Py·CO₂ of 47.4, 37.9, and 66.3 kcal/mol respectively, indicating that the anionic complex PyCOO^– stabilizes the anionic radicals CO₂ ^– and Py^– to facilitate low barrier ET. As the reduction of CO₂ proceeds through ET and then PT, the pyridine ring becomes aromatic, and thus Py catalyzes CO₂ reduction by stabilizing the PCET TS and the PyCOOH⁰ product through aromatic resonance stabilization. Our results suggest that Py catalyzes the homogeneous reductions of formic acid and formaldehyde en route to formation of CH₃OH through a series of one-electron reductions analogous to the PCET reduction of CO₂ examined here, where the electrode only acts to reduce PyH⁺ to PyH⁰

C–N Cross-Coupling via Photoexcitation of Nickel–Amine Complexes

C–N cross-coupling is an important class of reactions with far-reaching impacts across chemistry, materials science, biology, and medicine. Transition metal complexes can elegantly orchestrate diverse aminations but typically require demanding reaction conditions, precious metal catalysts, or oxygen-sensitive procedures. Here, we introduce a mild nickel-catalyzed C–N cross-coupling methodology that operates at room temperature using an inexpensive nickel source (NiBr₂·3H₂O), is oxygen tolerant, and proceeds through direct irradiation of the nickel–amine complex. This operationally robust process was employed for the synthesis of diverse C–N-coupled products (40 examples) by irradiating a solution containing an amine, an aryl halide, and a catalytic amount of NiBr₂·3H₂O with a commercially available 365 nm LED at room temperature without added photoredox catalyst and the amine substrate serving additional roles as the ligands and base. Density functional theory calculations and kinetic isotope effect experiments were performed to elucidate the observed C–N cross-coupling reactivity

Predicting Hydride Donor Strength via Quantum Chemical Calculations of Hydride Transfer Activation Free Energy

We propose a method to approximate the kinetic properties of hydride donor species by relating the nucleophilicity (<i>N</i>) of a hydride to the activation free energy <i>Δ<i>G</i></i>^⧧ of its corresponding hydride transfer reaction. <i>N</i> is a kinetic parameter related to the hydride transfer rate constant that quantifies a nucleophilic hydridic species’ tendency to donate. Our method estimates <i>N</i> using quantum chemical calculations to compute <i>Δ<i>G</i></i>^⧧ for hydride transfers from hydride donors to CO₂ in solution. A linear correlation for each class of hydrides is then established between experimentally determined <i>N</i> values and the computationally predicted <i>Δ<i>G</i></i>^⧧; this relationship can then be used to predict nucleophilicity for different hydride donors within each class. This approach is employed to determine <i>N</i> for four different classes of hydride donors: two organic (carbon-based and benzimidazole-based) and two inorganic (boron and silicon) hydride classes. We argue that silicon and boron hydrides are driven by the formation of the more stable Si–O or B–O bond. In contrast, the carbon-based hydrides considered herein are driven by the stability acquired upon rearomatization, a feature making these species of particular interest, because they both exhibit catalytic behavior and can be recycled

Organocatalyzed Birch Reduction Driven by Visible Light

The Birch reduction is a powerful synthetic methodology that uses solvated electrons to convert inert arenes to 1,4-cyclohexadienes—valuable intermediates for building molecular complexity. This reaction historically requires dangerous alkali metals and cryogenic liquid ammonia as the solvent, severely limiting application potential and scalability. Here, we introduce benzo[ghi]perylene imides as new organic photoredox catalysts for Birch reductions performed at ambient temperature and driven by visible light. Using low catalyst loadings (<1 mole percent), benzene and other functionalized arenes can be selectively transformed to 1,4-cyclohexadienes in good yields. Mechanistic studies support that this unprecedented visible light induced reactivity is enabled by the ability of the organic photoredox catalyst to harness the energy from two visible light photons to affect a single, high energy chemical transformation, likely proceeding through a solvated electron.</p

Dihydropteridine/Pteridine as a 2H⁺/2e^– Redox Mediator for the Reduction of CO₂ to Methanol: A Computational Study

Conflicting experimental results for the electrocatalytic reduction of CO₂ to CH₃OH on a glassy carbon electrode by the 6,7-dimethyl-4-hydroxy-2-mercaptopteridine have been recently reported [J. Am. Chem. Soc. 2014, 136, 14007−14010, J. Am. Chem. Soc. 2016, 138, 1017–1021]. In this connection, we have used computational chemistry to examine the issue of this molecule’s ability to act as a hydride donor to reduce CO₂. We first determined that the most thermodynamically stable tautomer of this aqueous compound is its oxothione form, termed here PTE. It is argued that this species electrochemically undergoes concerted 2H⁺/2e^– transfers to first form the kinetic product 5,8-dihydropteridine, followed by acid-catalyzed tautomerization to the thermodynamically more stable 7,8-dihydropteridine PTEH₂. While the overall conversion of CO₂ to CH₃OH by three successive hydride and proton transfers from this most stable tautomer is computed to be exergonic by 5.1 kcal/mol, we predict high activation free energies (Δ<i>G</i>^‡_HT) of 29.0 and 29.7 kcal/mol for the homogeneous reductions of CO₂ and its intermediary formic acid product by PTE/PTEH₂, respectively. These high barriers imply that PTE/PTEH₂ is unable, by this mechanism, to homogeneously reduce CO₂ on a time scale of hours at room temperature

Roles of the Lewis Acid and Base in the Chemical Reduction of CO₂ Catalyzed by Frustrated Lewis Pairs

We employ quantum chemical calculations to discover how frustrated Lewis pairs (FLP) catalyze the reduction of CO₂ by ammonia borane (AB); specifically, we examine how the Lewis acid (LA) and Lewis base (LB) of an FLP activate CO₂ for reduction. We find that the LA (trichloroaluminum, AlCl₃) alone catalyzes hydride transfer (HT) to CO₂ while the LB (trimesitylenephosphine, PMes₃) actually hinders HT; inclusion of the LB increases the HT barrier by ∼8 kcal/mol relative to the reaction catalyzed by LAs only. The LB hinders HT by donating its lone pair to the LUMO of CO₂, increasing the electron density on the C atom and thus lowering its hydride affinity. Although the LB hinders HT, it nonetheless plays a crucial role by stabilizing the active FLP·CO₂ complex relative to the LA dimer, free CO₂, and free LB. This greatly increases the concentration of the reactive complex in the form FLP·CO₂ and thus increases the rate of reaction. We expect that the principles we describe will aid in understanding other catalytic CO₂ reductions