Atom Transfer Reactions Research Articles

Formate Dehydrogenase Mimics as Catalysts for Carbon Dioxide Reduction.

Formate dehydrogenases (FDH) reversibly catalyze the interconversion of CO2 to formate. They belong to the family of molybdenum and tungsten-dependent oxidoreductases. For several decades, scientists have been synthesizing structural and functional model complexes inspired by these enzymes. These studies not only allow for finding certain efficient catalysts but also in some cases to better understand the functioning of the enzymes. However, FDH models for catalytic CO2 reduction are less studied compared to the oxygen atom transfer (OAT) reaction. Herein, we present recent results of structural and functional models of FDH.

Formation and Reactivity of a Fleeting NiIII Bisphenoxyl Diradical Species.

Cytochrome P450s and Galactose Oxidases exploit redox active ligands to form reactive high valent intermediates for oxidation reactions. This strategy works well for the late 3d metals where accessing high valent states is rather challenging. Herein, we report the oxidation of NiII (salen) (salen=N,N'-bis(3,5-di-tert-butyl-salicylidene)-1,2-cyclohexane-(1R,2R)-diamine) with mCPBA (meta-chloroperoxybenzoic acid) to form a fleeting NiIII bisphenoxyl diradical species, in CH3 CN and CH2 Cl2 at -40 °C. Electrochemical and spectroscopic analyses using UV/Vis, EPR, and resonance Raman spectroscopies revealed oxidation events both on the ligand and the metal centre to yield a NiIII bisphenoxyl diradical species. DFT calculations found the electronic structure of the ligand and the d-configuration of the metal center to be consistent with a NiIII bisphenoxyl diradical species. This three electron oxidized species can perform hydrogen atom abstraction and oxygen atom transfer reactions.

Formation and Reactivity of a Fleeting NiIII Bisphenoxyl Diradical Species

AbstractCytochrome P450s and Galactose Oxidases exploit redox active ligands to form reactive high valent intermediates for oxidation reactions. This strategy works well for the late 3d metals where accessing high valent states is rather challenging. Herein, we report the oxidation of NiII(salen) (salen=N,N′‐bis(3,5‐di‐tert‐butyl‐salicylidene)‐1,2‐cyclohexane‐(1R,2R)‐diamine) with mCPBA (meta‐chloroperoxybenzoic acid) to form a fleeting NiIII bisphenoxyl diradical species, in CH3CN and CH2Cl2 at −40 °C. Electrochemical and spectroscopic analyses using UV/Vis, EPR, and resonance Raman spectroscopies revealed oxidation events both on the ligand and the metal centre to yield a NiIII bisphenoxyl diradical species. DFT calculations found the electronic structure of the ligand and the d‐configuration of the metal center to be consistent with a NiIII bisphenoxyl diradical species. This three electron oxidized species can perform hydrogen atom abstraction and oxygen atom transfer reactions.

Sensitized photoreduction of selected benzophenones. Mass spectrometry studies of radical cross-coupling reactions

The hydrogen atom transfer reaction (HAT) between selected benzophenones (benzophenone BP, 3-carboxybenzophenone 3CB, and 4-carboxybenzophenone 4CB) and 2-propanol was reinvestigated focusing on stable product analysis. As expected, the primary species of these HAT's are the respective diphenyl and dimethyl ketyl radicals that eventually undergo several radical coupling reactions leading to stable photoproducts. However, the mechanisms of these free radical reactions remain unclear and open to question. In this report, we focus on the detailed analysis of the stable photoproducts of these reactions using liquid chromatography coupled with high-resolution mass spectrometry (LC-ESI-QTOF-MS/MS). Products of photopinacolization (benzpinacol and two diastereoisomers of 4CB and 3CB dimers) and isomeric radical cross-coupling adducts of respective diphenyl and dimethyl ketyl radicals were separated chromatographically, and their structures were determined by high-resolution MS/MS, and the mechanisms of the reactions are discussed.

Synthesis, Characterization, and the N Atom Transfer Reactivity of a Nitridochromium(V) Complex Stabilized by a Corrolato Ligand.

Metal complexes bearing nitrido ligands (M≡N) are at the forefront of current scientific research due to their resemblances with the metal complexes involved in the nitrogen fixation reactions. An oxo(corrolato)chromium(V) complex was used as a precursor complex for the facile synthesis of a new nitrido(corrolato)chromium(V) complex. The nitrido(corrolato)chromium(V) complex was characterized by various spectroscopic techniques. Density functional theory (DFT) calculations were performed on the nitrido(corrolato)chromium(V) complex to assign the vibrational and electronic transitions of this complex. The chromium–nitrogen (nitrido) bond distance obtained in the DFT-optimized structure is 1.530 Å and matches well with the earlier reported authentic Cr≡N bond distances obtained from the single-crystal X-ray diffraction data. This nitrido(corrolato)chromium(V) compound exhibited a sharp Soret band at 438 nm and a Q band at 608 nm. DFT calculations deliver that the origin of the bands at 438 and 608 nm is due to the intraligand charge transfer transitions. The nitrido(corrolato)chromium(V) complex showed one reversible oxidation and one reversible reduction couple at +0.53 and −0.06 V, respectively, vs the Ag/AgCl reference electrode. The simulation of the electron paramagnetic resonance data of the nitrido(corrolato)chromium(V) compound provided the following parameters: giso = 1.987, A53Cr = 26 G, and A14N = 2.71 G. From all these analyses, we can conclude that the electronic configuration in the native state of nitrido(corrolato)chromium(V) can be best described as [(cor3–)CrV(N3–)]−. Reactions of nitrido(corrolato)chromium(V) with the chloro(porphyrinato)chromium(III) complex resulted in a complete intermetal N atom transfer reaction between chromium corrole and chromium porphyrin complexes. A second-order rate constant of 4.29 ± 0.10 M–1 s–1 was obtained for this reaction. It was also proposed that this reaction proceeds via a bimetallic μ-nitrido intermediate.

Recent advances in total synthesis of natural products by masked ortho‐benzoquinones

AbstractThe Diels‐Alder adducts of masked ortho‐benzoquinone (MOB) normally perform high regio‐ and stereoselectivity and are generated under mild conditions. The advantages of MOB include: (a) Containing highly functional moieties: alkene, diene, carbonyl, enone, and dienone; (b) Easily accessible from 2‐methoxyphenol derivatives via oxidative dearomatization, and related 2‐methoxyphenol easily prepared from commercially available starting materials; (c) The Diels‐Alder adducts possessing unique features such as regio‐ and stereoselectivity and at least four contiguous stereogenic centers in one step. Furthermore, related bicyclo[2.2.2]octenone skeleton can be applied to further complex structure construction by various chemical transformations, such as radical cyclization, oxa‐di‐π‐methane rearrangement, Beckwith‐Dowd rearrangement, hydrogen atom transfer reaction, Cope rearrangement, Wanger‐Meerwein rearrangement, carbonyl‐ene reaction, aldol reaction, ring opening etc. Among these advantages, MOB system is prospected to continue as an important intermediate for total synthesis of natural products.

Effect of caffeic acid esters on antioxidant activity and oxidative stability of sunflower oil: Molecular simulation and experiments

Polyphenol, though used as antioxidants in food industry, suffers from poor solubility issues in vegetable oil. Usually, its solubility would be enhanced through esterification. This work investigated the antioxidant activity and oxidative stability of caffeic acid (CA) and its derivative modified esters by molecular simulation and experiments. Density functional theory (DFT) and molecular dynamic analysis revealed the antioxidant mechanism of CA esters attributing to the comprehensive effects. The lower hydrogen dissociation energy (ΔG) of CA esters with catechol moiety caused the transformation of antioxidant into quinone via the double hydrogen atom transfer reaction. Particularly, the second reduced hydrogen dissociation energy was the keypoint. The strong non-bond energy and hydrogen bond allowed CA esters and oil molecules to interact more efficiently. Hence, the ester moieties enhanced the antioxidant activity with 4.5–6.5 % ΔG reduction compared to CA. Rancimat and DSC assays validated the theoretical predictions. This result shows that the antioxidant activity of CA and its esters could be predicted by this molecular simulation way, which may aid in designing of new polyphenol antioxidant structure.

N − H bond dissociation free energy of a terminal iron phosphinimine

The transfer of protons and electrons to metal-ligand multiply-bonded species is a key step in the mechanism of many bond activation processes. In this regard, terminally-bonded phosphinimides (PN) are isolobal analogues of oxos and imidos and should enable late transition metal complexes featuring terminal PNs to engage in H+/e− transfer processes. Recently, we developed a rigid, multidentate PN framework intended to stabilize terminally bonded PN ligands at late, first row transition metals. Herein, we report the synthesis, structure, and spectroscopic characterization of mononuclear FeIII complexes featuring exclusively terminal PN coordination. Magnetic susceptibility and EPR spectroscopic data are consistent with S = 5/2 spin ground states. Proton transfer reactivity both via 1,2-addition across a PN − FeIII moiety and 1,2-elimination from a ferric phosphinimine (PNH) moiety is observed. Hydrogen atom transfer reactivity is observed upon oxidation of the PN − FeIII complex, resulting in formation of a PNH − FeIII species. A combination of electrochemical, pK a measurement, and DFT studies support an N − H bond dissociation free energy of ∼90 kcal/mol for a PNH − FeIII species, and serve to highlight a reactive, transient PN − FeIV species. Combined, our results highlight terminal, late transition metal-PN moieties as redox-active superbases competent for efficient hydrogen atom abstraction processes.

The access of {NiIV(OH)2} intermediate in Ni(II) mediated oxygen atom transfer to coordinated Phosphine: Combined experimental and computational studies

A tetranuclear Ni-complex of [(NiL)4] (1) (whereH2L = (E)-2-(((2-mercaptophenyl)imino)methyl)-6-methoxyphenol) was synthesized and fully characterized. The solvent dependent behaviour of 1 showed the existence of monomeric species which was well explained using several spectroscopic evidences. Compound [NiL(PPh3)] (2) and [LNi(dppe)NiL] (3) were synthesized by the reaction of 1 with respective phosphine in acetone (dppe = (Ph2PCH2CH2PPh2). All Ni-complexes were characterized by x-ray structure analysis and other spectroscopic techniques like 1H NMR, positive-ion ESI etc. The electrochemical responses for all Ni-complexes were explained. The reactivity of 2 and 3 with H2O2 and tBuOOH were explored in homogenous solution which identified that coordinated phosphine group at Ni(II) centre was oxidized and the reaction was preceded via oxygen atom transfer (OAT) reaction. The mechanism of OAT reaction of 2 with H2O2was proposed based on the detection of the intermediates using several possible spectroscopic tools and density functional theory (DFT) calculation approaches which demonstrated the highly exothermic nature of overall reaction (ΔGsol = -85.3 Kcal mol−1) and the reaction pathway involved the oxidative addition of H2O2 at Ni(II) center to form an intermediate Ni(IV)(OH)2 complex (INT1) followed by the reductive elimination of O = PPh3 occurred.

Factors Governing Reactivity and Selectivity in Hydrogen Atom Transfer from C(sp3)-H Bonds of Nitrogen-Containing Heterocycles to the Cumyloxyl Radical.

A kinetic study of the hydrogen atom transfer (HAT) reactions from nitrogen-containing heterocycles (secondary and tertiary lactams, 2-imidazolidinones, 2-oxazolidinones, and succinimides) to the cumyloxyl radical has been carried out employing laser flash photolysis with ns time resolution. HAT occurs from the C–H bonds that are α to nitrogen, activated by hyperconjugative overlap with the N–C=O π system. In the lactam series, the second-order HAT rate constant (kH) was observed to decrease by a factor of ∼4 going from the five- and six-membered ring derivatives to the eight-membered ones, a behavior that was rationalized on the basis of a reduced extent of hyperconjugative activation associated to the greater flexibility of the larger rings compared to the smaller ones. In the five-membered-ring substrate series, the kH values were observed to increase by >3 orders of magnitude on going from succinimide to 2-imidazolidinones, a behavior that was explained in terms of the divergent contribution of hyperconjugative activation and deactivating electronic effects determined by ring functionalities. The results are discussed in the framework of the development of HAT-based C–H bond functionalization procedures.

Experimental and Theoretical Examination of the Kinetic Isotope Effect in Cytochrome P450 Decarboxylase OleT.

Using a combination of experimental studies, theory, simulation, and modeling, we investigate the hydrogen atom transfer (HAT) reaction by the high-valent ferryl cytochrome P450 (CYP) intermediate known as Compound I, a species that is central to innumerable and important detoxification and biosynthetic reactions. The P450 decarboxylase known as OleT converts fatty acids, a sustainable biological feedstock, into terminal alkenes and thus is of high interest as a potential means to produce fungible biofuels. Previous experimental work has established the intermediacy of Compound I in the C─C scission reaction catalyzed by OleT and an unprecedented ability to monitor the HAT process in the presence of bound fatty acid substrates. Here, we leverage the kinetic simplicity of the OleT system to measure the activation barriers for CYP HAT and the temperature dependence of the substrate 2H kinetic isotope effect. Notably, neither measurement has been previously accessible for a CYP to date. Theoretical analysis alludes to the significance of substrate fatty acid coordination for generating the hydrogen donor/acceptor configurations that are most conducive for HAT to occur. The analysis of the two-dimensional potential energy surface, based on multireference electronic wave functions, illustrates the uncoupled character of the hydrogen motion. Quantum dynamics calculations along the hydrogen reaction path demonstrate that hydrogen tunneling is essential to qualitatively capture the experimental isotope effect, its temperature dependence, and appropriate activation energies. Overall, a more fundamental understanding of the OleT reaction coordinate contributes to the development of biomimetic catalysts for controlled C─H bond activation, an outstanding current challenge for (bio)synthetic chemistry.

Modeling the Ligand Effect on the Structure of CYP 450 Within the Density Functional Theory.

An improved understanding of the P450 structure is relevant to the development of biomimetic catalysts and inhibitors for controlled CH-bond activation, an outstanding challenge of synthetic chemistry. Motivated by the experimental findings of an unusually short Fe-S bond of 2.18 Å for the wild-type (WT) OleT P450 decarboxylase relative to a cysteine pocket mutant form (A369P), a computational model that captures the effect of the thiolate axial ligand on the iron-sulfur distance is presented. With the computational efficiency and streamlined analysis in mind, this model combines a cluster representation of the enzyme─40-110 atoms, depending on the heme and ligand truncation level─with a density functional theory (DFT) description of the electronic structure (ES) and is calibrated against the experimental data. The optimized Fe-S distances show a difference of 0.25 Å between the low and high spin states, in agreement with the crystallographic structures of the OleT WT and mutant forms. We speculate that this difference is attributable to the packing of the ligand; the mutant is bulkier due to an alanine-to-proline replacement, meaning that it is excluded from the energetically favored low-spin minimum because of steric constraints. The presence of pure spin-state pairs and the intersection of the low/high spin states for the enzyme model is indicative of the limitations of single-reference ES methods in such systems and emphasizes the significance of using the proper state when modeling the hydrogen atom transfer (HAT) reaction catalyzed by OleT. At the same time, the correct characterization of both the short and long Fe-S bonds within a small DFT-based model of 42 atoms paves the way for quantum dynamics modeling of the HAT step, which initiates the OleT decarboxylation reaction.

Photoinduced α‐C−H Amination of Cyclic Amine Scaffolds Enabled by Polar‐Radical Relay

AbstractHerein, we report a polar‐radical relay strategy for α‐C−H amination of cyclic amines with N‐chloro‐N‐sodio‐carbamates. The relay is initiated by in situ generation of cyclic iminium intermediate using N‐iodosuccinimide (NIS) oxidant as an initiator, which then operates through a series of polar (addition and elimination) and radical (homolysis, hydrogen‐ and halogen atom transfer) reactions to enable the challenging C−N bond formation in a controlled manner. A broad range of α‐amino cyclic amines were readily accessed with excellent regioselectivity, and the superb applicability was further demonstrated by functionalization of biologically relevant compounds.

Photoinduced α-C-H Amination of Cyclic Amine Scaffolds Enabled by Polar-Radical Relay.

Herein, we report a polar-radical relay strategy for α-C-H amination of cyclic amines with N-chloro-N-sodio-carbamates. The relay is initiated by in situ generation of cyclic iminium intermediate using N-iodosuccinimide (NIS) oxidant as an initiator, which then operates through a series of polar (addition and elimination) and radical (homolysis, hydrogen- and halogen atom transfer) reactions to enable the challenging C-N bond formation in a controlled manner. A broad range of α-amino cyclic amines were readily accessed with excellent regioselectivity, and the superb applicability was further demonstrated by functionalization of biologically relevant compounds.

Visible-Light-Induced α,γ-C(sp3)-H Difunctionalization of Piperidines.

Herein, we describe a novel protocol for visible-light-induced α,γ-C(sp3)-H difunctionalization of piperidines. This redox-neutral, atom-economical protocol, which exhibits a broad substrate scope and good functional group compatibility, constitutes a concise, practical method for constructing piperidine-containing bridged-ring molecules. Preliminary mechanistic studies indicated that highly regioselective activation of the inert γ-C(sp3)-H bond of piperidines was achieved through a 1,5-hydrogen atom transfer reaction of a nitrogen radical generated in situ.

Modeling the Reduction Kinetics of Munition Compounds by Humic Acids.

Dissolved organic matter (DOM) comprises a sizeable portion of the redox-active constituents in the environment and is an important reductant for the abiotic transformation of nitroaromatic compounds and munition constituents (NACs/MCs). Building a predictive kinetic model for these reactions would require the energies associated with both the reduction of the NACs/MCs and the oxidation of the DOM. The heterogeneous and unknown structure of DOM, however, has prohibited reliable determination of its oxidation energies. To overcome this limitation, humic acids (HAs) were used as model DOM, and their redox moieties were modeled as a collection of quinones of different redox potentials. The reduction and oxidation energies of the NACs/MCs and hydroquinones, respectively, via hydrogen atom transfer (HAT) reactions were then calculated quantum chemically. HAT energies have been used successfully in a linear free energy relationship (LFER) to predict second-order rate constants for NAC reduction by hydroquinones. Furthermore, a linear relationship between the HAT energies and the reduction potentials of quinones was established, which allows estimation of hydroquinone reactivity (i.e., rate constants) from HA redox titration data. A training set of three HAs and two NACs/MCs was used to generate a mean HA redox profile that successfully predicted reduction kinetics in multiple HA/MC systems.

Site-Selective C(sp3)–H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals

Site-Selective C(sp3)–H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals

Electrochemical Activation of C-C Bonds through Mediated Hydrogen Atom Transfer Reactions.

Activating inert sp3 -sp3 carbon-carbon (C-C) bonds remains a major bottleneck in the chemical upcycling of recalcitrant polyolefin waste. In this study, redox mediators are used to activate the inert C-C bonds. Specifically, N-hydroxyphthalimide (NHPI) is used as the redox mediator, which is oxidized to phthalimide-N-oxyl (PINO) radical to initiate hydrogen atom transfer (HAT) reactions with benzylic C-H bonds. The resulting carbon radical is readily captured by molecular oxygen to form a peroxide that decomposes into oxygenated C-C bond-scission fragments. This indirect approach reduces the oxidation potential by >1.2 V compared to the direct oxidation of the substrate. Studies with model compounds reveal that the selectivity of C-C bond cleavage increases with decreasing C-C bond dissociation energy. With NHPI-mediated oxidation, oligomeric styrene (OS510 ; Mn =510 Da) and polystyrene (PS; Mn ≈10 000 Da) are converted into oxygenated monomers, dimers, and oligomers.

Site-Selective C(sp3)–H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals

AbstractAmines and amides, as N-containing compounds, are ubiquitous in pharmaceutically-active scaffolds, natural products, agrochemicals, and peptides. Amides in nature bear a key responsibility for imparting three-dimensional structure, such as in proteins. Structural modifications to amines and amides, especially at their positions α to N, bring about profound changes in biological activity oftentimes leading to more desirable pharmacological profiles of small drug molecules. A number of recent developments in synthetic methodology for the functionalizations of amines and amides omit the need of their directing groups or pre-functionalizations, achieving direct activation of the otherwise relatively benign C(sp3)–H bonds α to N. Among these, hydrogen atom transfer (HAT) has proven a very powerful platform for the selective activation of amines and amides to their α-amino and α-amido radicals, which can then be employed to furnish C–C and C–X (X = heteroatom) bonds. The abilities to both form these radicals and control their reactivity in a site-selective manner is of utmost importance for such chemistries to witness applications in late-stage functionalization. Therefore, this review captures contemporary HAT strategies to realize chemo- and regioselective amine and amide α-C(sp3)–H functionalization, based on bond strengths, bond polarities, reversible HAT equilibria, traceless electrostatic-directing auxiliaries, and steric effects of in situ-generated HAT agents.1 Introduction2 Functionalizations of Amines3 Functionalizations of Carbamates4 Functionalizations of Amides5 Conclusion

Non-heme oxoiron complexes as active intermediates in the water oxidation process with hydrogen/oxygen atom transfer reactions.

In this study, we explore the water oxidation process with the help of density functional theory. The formation of an oxygen-oxygen bond is crucial in the water oxidation process. Here, we report the formation of the oxygen-oxygen bond by the N5-coordinate oxoiron species with a higher oxidation state of FeIV and FeV. This bond formation is studied through the nucleophilic addition of water molecules and the transfer of the oxygen atom from meta-chloroperbenzoic acid (mCPBA). Our study reveals that the oxygen-oxygen bond formation by reacting mCPBA with FeVO requires less activation barrier (13.7 kcal mol-1) than the other three pathways. This bond formation by the oxygen atom transfer (OAT) pathway is more favorable than that achieved by the hydrogen atom transfer (HAT) pathway. In both cases, the oxygen-oxygen bond formation occurs by interacting the σ*dz2-2pz molecular orbital of the iron-oxo intermediate with the 2px orbital of the oxygen atom. From this study, we understand that the oxygen-oxygen bond formation by FeIVO with the OAT process is also feasible (16 kcal mol-1), suggesting that FeVO may not always be required for the water oxidation process by non-heme N5-oxoiron. After the oxygen-oxygen bond formation, the release of the dioxygen molecule occurs with the addition of the water molecule. The release of dioxygen requires a barrier of 7.0 kcal mol-1. The oxygen-oxygen bond formation is found to be the rate-determining step.