Showing papers on "Homolysis published in 2021"

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis.

Abstract: We present here a review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms in which both an electron and a proton are exchanged together, often in a concerted elementary step. As such, MS-PCET can function as a non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from a wide variety of common organic functional groups. We present an introduction to MS-PCET and a practitioner's guide to reaction design, with an emphasis on the unique energetic and selectivity features that are characteristic of this reaction class. We then present chapters on oxidative N-H, O-H, S-H, and C-H bond homolysis methods, for the generation of the corresponding neutral radical species. Then, chapters for reductive PCET activations involving carbonyl, imine, other X═Y π-systems, and heteroarenes, where neutral ketyl, α-amino, and heteroarene-derived radicals can be generated. Finally, we present chapters on the applications of MS-PCET in asymmetric catalysis and in materials and device applications. Within each chapter, we subdivide by the functional group undergoing homolysis, and thereafter by the type of transformation being promoted. Methods published prior to the end of December 2020 are presented.

Visible-Light-Induced Homolysis of Earth-Abundant Metal-Substrate Complexes: A Complementary Activation Strategy in Photoredox Catalysis.

Abstract: The mainstream applications of visible-light photoredox catalysis predominately involve outer-sphere single-electron transfer (SET) or energy transfer (EnT) processes of precious metal RuII or IrIII complexes or of organic dyes with low photostability. Earth-abundant metal-based Mn Ln -type (M=metal, Ln =polydentate ligands) complexes are rapidly evolving as alternative photocatalysts as they offer not only economic and ecological advantages but also access to the complementary inner-sphere mechanistic modes, thereby transcending their inherent limitations of ultrashort excited-state lifetimes for use as effective photocatalysts. The generic process, termed visible-light-induced homolysis (VLIH), entails the formation of suitable light-absorbing ligated metal-substrate complexes (Mn Ln -Z; Z=substrate) that can undergo homolytic cleavage to generate Mn-1 Ln and Z. for further transformations.

C(sp 3 )-H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling.

Abstract: The "magic methyl" effect describes the change in potency, selectivity, and/or metabolic stability of a drug candidate associated with addition of a single methyl group. We report a synthetic method that enables direct methylation of C(sp3)-H bonds in diverse drug-like molecules and pharmaceutical building blocks. Visible light-initiated triplet energy transfer promotes homolysis of the O-O bond in di-tert-butyl or dicumyl peroxide under mild conditions. The resulting alkoxyl radicals undergo divergent reactivity, either hydrogen-atom transfer from a substrate C-H bond or generation of a methyl radical via β-methyl scission. The relative rates of these steps may be tuned by varying the reaction conditions or peroxide substituents to optimize the yield of methylated product arising from nickel-mediated cross-coupling of substrate and methyl radicals.

Diastereoselective Synthesis of Aryl C-Glycosides from Glycosyl Esters via C−O Bond Homolysis

Abstract: C -aryl glycosyl compounds offer better in vivo stability relative to O- and N- glycoside analogues. C -aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C -aryl glycosides are derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional group compatibility, and practicality. Challenges remain in the synthesis of C -aryl nucleosides and 2-deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross-coupling method to prepare C -aryl and heteroaryl glycosides, including nucleosides and 2-deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C-O bond homolysis. This strategy represents a new means to activate alcohols as a cross-coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.

BonDNet: a graph neural network for the prediction of bond dissociation energies for charged molecules.

Abstract: A broad collection of technologies, including e.g. drug metabolism, biofuel combustion, photochemical decontamination of water, and interfacial passivation in energy production/storage systems rely on chemical processes that involve bond-breaking molecular reactions. In this context, a fundamental thermodynamic property of interest is the bond dissociation energy (BDE) which measures the strength of a chemical bond. Fast and accurate prediction of BDEs for arbitrary molecules would lay the groundwork for data-driven projections of complex reaction cascades and hence a deeper understanding of these critical chemical processes and, ultimately, how to reverse design them. In this paper, we propose a chemically inspired graph neural network machine learning model, BonDNet, for the rapid and accurate prediction of BDEs. BonDNet maps the difference between the molecular representations of the reactants and products to the reaction BDE. Because of the use of this difference representation and the introduction of global features, including molecular charge, it is the first machine learning model capable of predicting both homolytic and heterolytic BDEs for molecules of any charge. To test the model, we have constructed a dataset of both homolytic and heterolytic BDEs for neutral and charged (-1 and +1) molecules. BonDNet achieves a mean absolute error (MAE) of 0.022 eV for unseen test data, significantly below chemical accuracy (0.043 eV). Besides the ability to handle complex bond dissociation reactions that no previous model could consider, BonDNet distinguishes itself even in only predicting homolytic BDEs for neutral molecules; it achieves an MAE of 0.020 eV on the PubChem BDE dataset, a 20% improvement over the previous best performing model. We gain additional insight into the model's predictions by analyzing the patterns in the features representing the molecules and the bond dissociation reactions, which are qualitatively consistent with chemical rules and intuition. BonDNet is just one application of our general approach to representing and learning chemical reactivity, and it could be easily extended to the prediction of other reaction properties in the future.

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides.

Abstract: Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.

Bismuth Amides Mediate Facile and Highly Selective Pn–Pn Radical-Coupling Reactions (Pn=N, P, As)

Abstract: The controlled release of well‐defined radical species under mild conditions for subsequent use in selective reactions is an important and challenging task in synthetic chemistry. We show here that simple bismuth amide species [Bi(NAr\(_2\))\(_3\)] readily release aminyl radicals [NAr\(_2\)]. at ambient temperature in solution. These reactions yield the corresponding hydrazines, Ar\(_2\)N−NAr\(_2\), as a result of highly selective N−N coupling. The exploitation of facile homolytic Bi−Pn bond cleavage for Pn−Pn bond formation was extended to higher homologues of the pnictogens (Pn=N–As): homoleptic bismuth amides mediate the highly selective dehydrocoupling of HPnR\(_2\) to give R\(_2\)Pn−PnR\(_2\). Analyses by NMR and EPR spectroscopy, single‐crystal X‐ray diffraction, and DFT calculations reveal low Bi−N homolytic bond‐dissociation energies, suggest radical coupling in the coordination sphere of bismuth, and reveal electronic and steric parameters as effective tools to control these reactions.

Photocatalytic Anti-Markovnikov Radical Hydro- and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

Abstract: A tunable photocatalytic method is reported for anti-Markovnikov hydro- and aminooxygenation of unactivated alkenes using readily accessible ketoxime carbonates as the diverse functionalization reagents. Mechanistic studies reveal that this reaction is initiated through an energy-transfer-promoted N-O bond homolysis of ketoxime carbonates leading to alkoxylcarbonyloxyl and iminyl radicals under visible-light photocatalysis, followed by the addition of alkoxylcarbonyloxyl radical to alkenes. By taking advantage of the different stability of the iminyl radicals, the generated carbon radical either abstracts a hydrogen atom from the media to form the anti-Markovnikov hydrooxygenation product, or it is trapped by the persistent iminyl radical to furnish the aminooxygenation product. Notably, this is the first example of direct hydrooxygenation of unactivated olefins with anti-Markovnikov regioselectivity involving an oxygen-centered radical.

Renaissance of Homogeneous Cerium Catalysts with Unique Ce(IV/III) Couple: Redox-Mediated Organic Transformations Involving Homolysis of Ce(IV)-Ligand Covalent Bonds.

Abstract: Recent advances in the catalytic application of cerium complexes were achieved through controlling the Ce(IV/III) redox couple. Although Ce(IV) complexes have been extensively investigated as stoichiometric oxidants in organic synthesis on the basis of their highly positive redox potentials, these complexes can be used as catalysts, not only by introducing supporting ligands around the coordination sphere of cerium, but also by taking advantage of the photoresponsive properties of Ce(IV) and Ce(III) species. Cerium is highly abundant, comparable to that of some first-row transition metals such as copper, nickel, and zinc. Cerium complexes are new and promising homogeneous catalyst candidates for a variety of organic transformations under mild reaction conditions. They are typically used to activate dioxygen to oxidize organic compounds and applied for organic radical generation using the photoresponsive character of Ce(IV) carboxylates and alkoxides as well as electronic transition of Ce(III), in which homolysis of Ce(IV)-ligand covalent bonds is an important step for the overall catalytic cycle. In this Perspective, we first review the early discovery of Ce(OAc)4-mediated oxidative transformations to emphasize the importance of Ce(IV)-OAc bond homolysis in various C-C bond-forming reactions and its relation to recent developments. We then focus on the fundamental importance of Ce(IV) reactivity involving thermal and photoassisted homolysis of the Ce(IV)-ligand covalent bond and the developments regarding Ce(IV/III) redox changes in catalytic reactions together with our recent findings on cerium-based catalysis.

1- and 2-Azetines via Visible Light-Mediated [2 + 2]-Cycloadditions of Alkynes and Oximes.

Abstract: Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development but remain underexplored due to challenges associated with their synthesis. We report an efficient, visible light-mediated approach toward 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular [2 + 2]-cycloaddition via triplet energy transfer from a commercially available iridium photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process. Mechanistic studies are consistent with a stepwise reaction mechanism via N-O bond homolysis following the second energy transfer event to result in the formation of 1-azetine products. Characteristic for this method is its operational simplicity, mild conditions, and modular approach that allow for the synthesis of functionalized azetines and tetrahydrofurans (via in situ hydrolysis) from readily available precursors.

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp3)-H Bonds with Zhdankin's λ3-Azidoiodane.

Abstract: An in-depth study of the mechanism of the azidation of C(sp3)-H bonds with Zhdankin's λ3-azidoiodane reagent catalyzed by iron(II)(pybox) complexes is reported. Previously, it was shown that tertiary and benzylic C(sp3)-H bonds of a range of complex molecules underwent highly site-selective azidation by reaction with a λ3-azidoiodane reagent and an iron(II)(pybox) catalyst under mild conditions. However, the mechanism of this reaction was unclear. Here, a series of mechanistic experiments are presented that reveal critical features responsible for the high selectivity and broad scope of this reaction. These experiments demonstrate the ability of the λ3-azidoiodane reagent to undergo I-N bond homolysis under mild conditions to form λ2-iodanyl and azidyl radicals that undergo highly site-selective and rate-limiting abstraction of a hydrogen atom from the substrate. The resultant alkyl radical then combines rapidly with a resting state iron(III)-azide complex, which is generated by the reaction of the λ3-azidoiodane with the iron(II)(pybox) complex, to form the C(sp3)-N3 bond. This mechanism is supported by the independent synthesis of well-defined iron complexes characterized by cyclic voltammetry, X-ray diffraction, and EPR spectroscopy, and by the reaction of the iron complexes with alkanes and the λ3-azidoiodane. Reaction monitoring and kinetic studies further reveal an unusual effect of the catalyst on the rate of formation of product and consumption of reactants and suggest a blueprint for the development of new processes leading to late-stage functionalization of C(sp3)-H bonds.

A DFT-based microkinetic study on methanol synthesis from CO2 hydrogenation over the In2O3 catalyst

Abstract: In this work, we performed density functional theory (DFT)-based microkinetic simulations to elucidate the reaction mechanism of methanol synthesis on two of the most stable facets of the cubic In2O3 (c-In2O3) catalyst, namely the (111) and (110) surfaces. Our DFT calculations show that for both surfaces, it is difficult for the H atom adsorbed at the remaining surface O atom around the O vacancy (Ov) active site to migrate to an O adsorbed at the Ov due to the very high energy barrier involved. In addition, we also find that the C–O bond in the bt-CO2* chemisorption structure can directly break to form CO with a lower energy barrier than that in its hydrogenation to the COOH* intermediate in the COOH route. However, our microkinetic simulations suggest that for both surfaces, CO2 deoxygenation to form CO in both pathways, namely the COOH and CO–O routes, are kinetically slower than methanol formation under typical steady state conditions assuming a CO2 conversion of 10% and a CO selectivity of 1%. Although these results agree with previous experimental observations at relatively low reaction temperature, where methanol formation dominates, they cannot explain the predominant formation of CO at relatively high reaction temperature. We tentatively attribute this to the simplicity of our microkinetic model as well as possible structural changes of the catalyst at relatively high reaction temperature. Furthermore, although the rate-determining step (RDS) from the degree of rate control (DRC) analysis is usually consistent with that judged from the DFT calculated energy barriers, for CO2 hydrogenation to methanol over the (111) surface, our DRC analysis suggests homolytic H2 dissociation to be the rate-controlling step, which is not apparent from the DFT-calculated energy barriers. This indicates that CO2 conversion and methanol selectivity over the (111) surface can be further enhanced if homolytic H2 dissociation can be accelerated for instance by introducing transition metal dopants as already shown by some experimental observations.

Radical 1,4-Aryl Migration Enabled Remote Cross-Electrophile Coupling of α-Amino-β-Bromo Acid Esters with Aryl Bromides.

Abstract: We report an unprecedented, efficient nickel-catalysed radical relay for the remote cross-electrophile coupling of β-bromo-α-benzylamino acid esters with aryl bromides via 1,4-aryl migration/arylation cascades. β-Bromo-α-benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce-Smiles rearrangement. This reaction enables the formation of two new C(sp3 )-C(sp2 ) bonds using a bench-stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox-neutral C(sp3 )-C(sp2 ) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross-electrophile coupling and radical 1,4-aryl migration through the generation of C(sp3 )-centred radical intermediates from the homolysis of C(sp3 )-Br bonds and the switching of the transient alkyl radical into a robust α-aminoalkyl radical.

Cooperative Hydrogen Atom Transfer: From Theory to Applications

Abstract: Hydrogen atom transfer (HAT) is one of the fundamental transformations of organic chemistry, allowing the interconversion of open- and closed-shell species through the concerted movement of a proton and an electron. Although the value of this transformation is well appreciated in isolation, with it being used for homolytic C–H activation via abstractive HAT and radical reduction via donative HAT, cooperative HAT (cHAT) reactions, in which two hydrogen atoms are removed or donated to vicinal reaction centers in succession through radical intermediates, are comparatively unknown outside of the mechanism of desaturase enzymes. This tandem reaction scheme has important ramifications in the thermochemistry of each HAT, with the bond dissociation energy (BDE) of the C–H bond adjacent to the radical center being significantly lowered relative to that of the parent alkane, allowing each HAT to be performed by different species. Herein, we discuss the thermodynamic basis of this bond strength differential in cHAT and demonstrate its use as a design principle in organic chemistry for both dehydrogenative (application 1) and hydrogenative (application 2) reactions. We hope that this overview will highlight the exciting reactivity that is possible with cHAT and inspire further developments with this mechanistic approach. 1 Introduction and Theory 2 Application: Dehydrogenative Transformations 3 Application: Alkene Hydrogenation 4 Future Applications of cHAT

Heterolytic Bond Cleavage in a Scissile Triarylmethane Mechanophore.

Abstract: Covalent mechanophores display the cleavage of a weak covalent bond when a sufficiently high mechanical force is applied. Three different covalent bond breaking mechanisms have been documented thus far, including concerted, homolytic, and heterolytic scission. Motifs that display heterolytic cleavage typically separate according to non-scissile reaction pathways that afford zwitterions. Here, we report a new mechanochromic triarylmethane mechanophore, which dissociates according to a scissile heterolytic pathway and displays a pronounced mechanochromic response. The mechanophore was equipped with two styrenylic handles that allowed its incorporation as a cross-linker into poly(N,N-dimethylacrylamide) and poly(methyl acrylate-co-2-hydroxyethyl acrylate) networks. These materials are originally colorless, but compression or tensile deformation renders the materials colored. By combining tensile testing and in situ transmittance measurements, we show that this effect is related to scissile cleavage leading to colored triarylmethane carbocations.

Impact of the macrocyclic structure and dynamic solvent effect on the reactivity of a localised singlet diradicaloid with π-single bonding character

Abstract: Localised singlet diradicals are key intermediates in bond homolysis processes. Generally, these highly reactive species undergo radical–radical coupling reaction immediately after their generation. Therefore, their short-lived character hampers experimental investigations of their nature. In this study, we implemented the new concept of “stretch effect” to access a kinetically stabilised singlet diradicaloid. To this end, a macrocyclic structure was computationally designed to enable the experimental examination of a singlet diradicaloid with π-single bonding character. The kinetically stabilised diradicaloid exhibited a low carbon–carbon coupling reaction rate of 6.4 × 103 s−1 (155.9 μs), approximately 11 and 1000 times slower than those of the first generation of macrocyclic system (7.0 × 104 s−1, 14.2 μs) and the parent system lacking the macrocycle (5 × 106 s−1, 200 ns) at 293 K in benzene, respectively. In addition, a significant dynamic solvent effect was observed for the first time in intramolecular radical–radical coupling reactions in viscous solvents such as glycerin triacetate. This theoretical and experimental study demonstrates that the stretch effect and solvent viscosity play important roles in retarding the σ-bond formation process, thus enabling a thorough examination of the nature of the singlet diradicaloid and paving the way toward a deeper understanding of reactive intermediates.

Active-Site Controlled, Jahn-Teller Enabled Regioselectivity in Reductive S-C Bond Cleavage of S-Adenosylmethionine in Radical SAM Enzymes.

Abstract: Catalysis by canonical radical S-adenosyl-l-methionine (SAM) enzymes involves electron transfer (ET) from [4Fe-4S]+ to SAM, generating an R3S0 radical that undergoes regioselective homolytic reductive cleavage of the S-C5' bond to generate the 5'-dAdo· radical. However, cryogenic photoinduced S-C bond cleavage has regioselectively yielded either 5'-dAdo· or ·CH3, and indeed, each of the three SAM S-C bonds can be regioselectively cleaved in an RS enzyme. This diversity highlights a longstanding central question: what controls regioselective homolytic S-C bond cleavage upon SAM reduction? We here provide an unexpected answer, founded on our observation that photoinduced S-C bond cleavage in multiple canonical RS enzymes reveals two enzyme classes: in one, photolysis forms 5'-dAdo·, and in another it forms ·CH3. The identity of the cleaved S-C bond correlates with SAM ribose conformation but not with positioning and orientation of the sulfonium center relative to the [4Fe-4S] cluster. We have recognized the reduced-SAM R3S0 radical is a (2E) state with its antibonding unpaired electron in an orbital doublet, which renders R3S0 Jahn-Teller (JT)-active and therefore subject to vibronically induced distortion. Active-site forces induce a JT distortion that localizes the odd electron in a single priority S-C antibond, which undergoes regioselective cleavage. In photolytic cleavage those forces act through control of the ribose conformation and are transmitted to the sulfur via the S-C5' bond, but during catalysis thermally induced conformational changes that enable ET from a cluster iron generate dominant additional forces that specifically select S-C5' for cleavage. This motion also can explain how 5'-dAdo· subsequently forms the organometallic intermediate Ω.

Electrostatic Perturbations from the Protein Affect C-H Bond Strengths of the Substrate and Enable Negative Catalysis in the TmpA Biosynthesis Enzyme

Abstract: The nonheme iron dioxygenase 2-(trimethylammonio)-ethylphosphonate dioxygenase (TmpA) is an enzyme involved in the regio- and chemoselective hydroxylation at the C 1 -position of the substrate as part of the biosynthesis of glycine betaine in bacteria and carnitine in humans. To understand how the enzyme avoids breaking the weak C 2 -H bond in favor of C 1 -hydroxylation, we set up a cluster model of 242 atoms representing the first and second-coordination sphere of the metal center and substrate binding pocket and investigated possible reaction mechanisms of substrate activation by an iron(IV)-oxo species by density functional theory methods. In agreement with experimental product distributions, the calculations predict a favorable C 1 -hydroxylation pathway. The calculations show that the selectivity is guided through electrostatic perturbations inside the protein from charged residues, external electric fields and electric dipole moments. In particular, charged residues influence and perturb the homolytic bond strength of the C 1 -H and C 2 -H bonds of the substrate, and strongly strengthens the C 2 -H bond in the substrate-bound orientation.

1- and 2-Azetines via Visible Light-Mediated [2+2]-Cycloadditions of Alkynes and Oximes

Abstract: Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development, but remain underexplored due to challenges associated with their synthesis. We report an efficient, visible light-mediated approach to-wards 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular [2+2]-cycloaddition via triplet energy transfer from a commercially available iridi-um photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process. Mechanistic studies are consistent with a stepwise reaction mechanism via N-O bond homolysis following the second energy transfer event to result in the formation of 1-azetine products. Characteristic for this method is its operational simplicity, mild conditions and modular approach that allows for the synthesis of functionalized azetines and tetrahydrofurans via in situ hydrolysis from readily available precursors.

The Chemical Bond: When Atom Size instead of Electronegativity Difference Determines Trend in Bond Strength

Abstract: We have quantum chemically analyzed element-element bonds of archetypal Hn X-YHn molecules (X, Y=C, N, O, F, Si, P, S, Cl, Br, I), using density functional theory. One purpose is to obtain a set of consistent homolytic bond dissociation energies (BDE) for establishing accurate trends across the periodic table. The main objective is to elucidate the underlying physical factors behind these chemical bonding trends. On one hand, we confirm that, along a period (e. g., from C-C to C-F), bonds strengthen because the electronegativity difference across the bond increases. But, down a period, our findings constitute a paradigm shift. From C-F to C-I, for example, bonds do become weaker, however, not because of the decreasing electronegativity difference. Instead, we show that the effective atom size (via steric Pauli repulsion) is the causal factor behind bond weakening in this series, and behind the weakening in orbital interactions at the equilibrium distance. We discuss the actual bonding mechanism and the importance of analyzing this mechanism as a function of the bond distance.

Nickel-Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long-Range Electron Transfer

Abstract: Methyl-coenzyme M reductase (MCR) catalyzes both the synthesis and the anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of cofactor F430. The Ni ion, in its low-valent Ni(I) state, lights the fuse leading to homolysis of the C-S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. On the basis of the crystal structures, which reveal a Ni-thiol interaction between Ni(II)-MCR and inhibitor CoMSH, a Ni(I)-thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)-disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)-sulfur interaction poses a conundrum for the proposed hydrogen-atom abstraction reaction because the >6 A distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears to be too long for such a reaction. The spectroscopic, kinetic, structural, and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)-N/O complex, not Ni(I)-S. These studies rule out direct Ni(I)-sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both the forward and the reverse MCR reactions emanate through long-range electron transfer from the Ni(I)-sulfonate complexes with methyl-SCoM and CoMSSCoB, respectively.

Selective Bond Cleavage in RAFT Agents Promoted by Low-Energy Electron Attachment.

Abstract: Radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization) has been successfully applied to generate polymers of well-defined architecture. For RAFT polymerization a source of radicals is required. Recent work has demonstrated that for minimal side-reactions and high spatio-temporal control these should be formed directly from the RAFT agent or macroRAFT agent (usually carbonothiosulfanyl compounds) thermally, photochemically or by electrochemical reduction. In this work, we investigated low-energy electron attachment to a common RAFT agent (cyanomethyl benzodithioate), and, for comparison, a simple carbonothioylsulfanyl compound (dimethyl trithiocarbonate, DMTTC) in the gas phase by means of mass spectrometry as well as quantum chemical calculations. We observe for both compounds that specific cleavage of the C-S bond is induced upon low-energy electron attachment at electron energies close to zero eV. This applies even in the case of a poor homolytic leaving group (. CH3 in DMTTC). All other dissociation reactions found at higher electron energies are much less abundant. The present results show a high control of the chemical reactions induced by electron attachment.

Photoinduced Atom Transfer Radical Addition Reaction of Olefins with α-Bromo Carbonyls.

Abstract: The irradiation of halogen-bonded complexes with light leads to the homolysis of carbon-halogen bonds and the formation of the corresponding carbon radical species. However, the only methodology reported for these halogen-bonding complexes is using CBr4 as the halogen-bond donor and its applicability is of great interest. In this study, the atom transfer radical addition (ATRA) reaction of olefins using bromomalonates as halogen-bonding donors was developed. Using 4-phenylpyridine as the halogen-bonding acceptor, the desired reaction proceeded well under external irradiation of 380 nm light to furnish the corresponding ATRA reaction product. The ATRA reaction was effective in generating the corresponding products for a variety of olefins. Furthermore, the ATRA reaction was applicable to bulky ketones, substrates, and malonate esters. The intermediates of the reaction were identified and a plausible reaction mechanism was proposed.