H-atom Transfer Research Articles

Mechanistic studies on the oxidation reaction of n-pentane

The oxidation reaction mechanism of n-pentane is investigated using density functional theory and transition state theory as a case study to elucidate the combustion characteristics of liquids with low boiling points. This study divides the oxidation reaction of n-pentane into four steps. First, n-pentane decomposes to form n-pentyl radicals C5H11 and H, CH3 and C4H9, and C2H5 and C3H7 radicals. Second, n-pentane primarily undergoes H-abstraction reactions with H, CH3, C2H5, and C3H7 radicals to form the C5H11 radicals. Subsequently, C5H11 radicals react with O2 in an addition reaction to form n-pentyl peroxy radicals ROO. Finally, ROO radical undergoes internal H-atom transfer to form hydroperoxy pentyl radicals QOOH, which then undergoes cyclization and bond scission to produce cyclic ethers, alkenes, aldehydes, OH radicals, and HO2 radicals. Results indicate that n-pentane readily decomposes into C2H5 and C3H7 radicals, with a bond dissociation energy of 367.1 KJ/mol. The H-abstraction reactions involving H and CH3 radicals have the fastest rates, which require the lowest energy barriers of 21.6 and 41.9 KJ/mol, respectively. The reaction between C5H11 and O2 is a barrierless addition reaction. The oxidation of n-pentane, which leads to the formation of 2-methyloxirane and OH radicals, exhibits the fastest reaction rate.

Interception and Synthetic Application of Diradical and Diene Forms of Dual-Nature Azabicyclic o-Quinodimethanes Generated by 6π-Azaelectrocyclization.

We demonstrate that 2-alkenylarylaldimines and ketimines undergo thermal 6π-azaelectrocyclization to generate a wide range of azabicyclic o-quinodimethanes (o-QDMs). These o-QDMs exist as a hybrid of a diene and a benzylic diradical. The diradical nature was confirmed by their ability to undergo dimerization and react with H-atom donor, 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) and O2. In addition, the interception of the diradicaloid o-QDMs by H-atom transfer was used to synthesize five tetrahydroisoquinoline alkaloids and related bioactive molecules. The diene form can undergo [4+2] cycloaddition reactions with different dienophiles to generate bridged azabicycles in high endo:exo selectivity. The azabicyclic o-QDMs can be generated for [4+2] cycloaddition from a wide range of electronically and sterically varied 2-alkenylarylimines, including mono, di, tri and tetrasubstituted alkenes, and imines derived from arylamine, alkylamine (1°, 2°, 3°), benzylamine, benzylsulfonamide and Boc-amine.

Dual-Catalytic Structural Isomerisation as a Route to α-Arylated Ketones.

Isomerisation reactions provide streamlined routes to organic compounds which are otherwise hard to directly synthesise. The most common forms are positional, geometrical or stereochemical isomerisations which involve the relocation of a double bond or a change in relative location of groups in space. In contrast, far fewer examples of structural (or constitutional) isomerisation exist where the connectivity between atoms is altered. The development of platforms capable of such rearrangement poses a unique set of challenges because chemical bonds must be selectively cleaved, and new ones formed without overall addition or removal of atoms. Here, we show that a dual catalytic system can enable the structural isomerisation of readily available allylic alcohols into more challenging-to-synthesise α-arylated ketones via a H-atom transfer initiated semi-pinacol rearrangement. Key to our strategy is the combination of a cobalt catalyst and photocatalyst under reductive, protic conditions which allows intermediates to propagate catalytic turnover. By providing an unusual disconnection to structural motifs which are difficult to access through direct arylation, we anticipate inspiring other advanced catalytic isomerisation strategies that will further retrosynthetic logic for complex molecule synthesis.

An evolved artificial radical cyclase enables the construction of bicyclic terpenoid scaffolds via an H-atom transfer pathway.

While natural terpenoid cyclases generate complex terpenoid structures via cationic mechanisms, alternative radical cyclization pathways are underexplored. The metal-catalysed H-atom transfer reaction (M-HAT) offers an attractive means for hydrofunctionalizing olefins, providing access to terpenoid-like structures. Artificial metalloenzymes offer a promising strategy for introducing M-HAT reactivity into a protein scaffold. Here we report our efforts towards engineering an artificial radical cyclase (ARCase), resulting from anchoring a biotinylated [Co(Schiff-base)] cofactor within an engineered chimeric streptavidin. After two rounds of directed evolution, a double mutant catalyses a radical cyclization to afford bicyclic products with a cis-5-6-fused ring structure and up to 97% enantiomeric excess. The involvement of a histidine ligation to the Co cofactor is confirmed by crystallography. A time course experiment reveals a cascade reaction catalysed by the ARCase, combining a radical cyclization with a conjugate reduction. The ARCase exhibits tolerance towards variations in the dienone substrate, highlighting its potential to access terpenoid scaffolds.

Resolving Conflicting Mechanisms for Photoredox Allylic sp3-CH Arylation Using Deuterium-Labeling and Isotope Effects.

Two conflicting mechanisms have emerged for the direct arylation of allylic C-H bonds enabled by the combined use of thiol and photoredox catalysis. In the original report (Nature, 2015, 519, 74-77), a radical coupling step-between a radical anion of an arene and an allylic radical-is proposed to be the key C-C bond-forming step. A recent mechanistic study (J. Org. Chem. 2022, 87, 223-230) has suggested that the C-C bond formation occurs via radical anion capture by the olefin followed by an H atom transfer (HAT) event to deliver the allylic C-H arylation product. Utilizing cyclohexene-4,4,5,5-d 4 as a mechanistic probe to distinguish between otherwise indistinguishable regioisomeric allylic C-H arylation products in the reaction of cyclohexene and dicyanobenzene, we establish that the radical anion capture-HAT mechanism is not operative. Furthermore, experimental k H/k D studies and DFT calculations lend strong support to the radical coupling mechanism proceeding via irreversible HAT to form the allylic radical of cyclohexene, followed by regioselectivity-determining radical coupling (for unsymmetrical olefins) and facile decyanation.

Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer.

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion of low energy starting materials such as H2O and CO2 into higher energy products in the form of carbohydrates and O2. While this model for utilizing light-driven charge transfer to drive catalytic reactions thermodynamically "uphill" has been extensively adapted for small molecule activation, molecular machines, photoswitches, and solar fuel chemistry, its application in organic synthesis has been less systematically developed. However, the potential benefits of these approaches are significant, both in enabling transformations that cannot be readily achieved using conventional thermal chemistry and in accessing distinct selectivity regimes that are uniquely enabled by excited-state mechanisms. In this Account, we present work from our group that highlights the ability of visible light photoredox catalysis to drive useful organic transformations away from their equilibrium positions, addressing a number of long-standing synthetic challenges.We first discuss how excited-state ET enabled the first general methods for the catalytic anti-Markovnikov hydroamination of unactivated alkenes with alkyl amines. In these reactions, an excited-state iridium(III) photocatalyst reversibly oxidizes secondary amine substrates to their corresponding aminium radical cations (ARCs). These electrophilic N-centered radicals can then react with olefins to furnish valuable tertiary amine products with complete anti-Markovnikov regioselectivity. Notably, some of these products are less thermodynamically stable than their corresponding amine and alkene starting materials. We next present a strategy for light-driven C-C bond cleavage within various aliphatic alcohols mediated by homolytic activation of alcohol O-H bonds by excited-state proton-coupled electron transfer (PCET). The resulting alkoxy radical intermediates then undergo C-C β-scission to ultimately provide isomeric linear carbonyl products that are often higher in energy than their cyclic alcohol precursors. Applications of this chemistry for the light-driven depolymerization of lignin biomass, commercial phenoxy resin, hydroxylated polyolefin derivatives, and thermoset polymers are presented as well. We then describe a method for the contrathermodynamic positional isomerization of highly substituted olefins by means of cooperative photoredox and chromium(II) catalysis. In this work, generation of an allylchromium(III) species that can undergo highly regioselective in situ protodemetalation enables access to a less substituted and thermodynamically less stable positional isomer. Product selectivity in this reaction is determined by the large differential in oxidation potentials between differently substituted olefin isomers. Lastly, we discuss a light-driven deracemization reaction developed in collaboration with the Miller group, wherein a racemic urea substrate undergoes spontaneous optical enrichment upon visible light irradiation in the presence of an iridium(III) chromophore, a chiral Brønsted base, and a chiral peptide thiol. Excellent levels of enantioselectivity are achieved via sequential and synergistic proton transfer (PT) and H atom transfer (HAT) steps. Taken together, these examples highlight the ability of excited-state ET events to enable access to nonequilibrium product distributions across a wide range of catalytic, redox-neutral transformations in which photons are the only stoichiometric reagents.

Dynamics of the Decomposition of Gas Molecules Containing Sulfur and Nitrogen from Char-S and Char-N Structures in Combustion and Pyrolysis Reactions

ABSTRACT Combustion states of char-S (C14H16O4S) and char-N (C18H19NO3) sub function molecules in a limited number of oxygen environments and pyrolysis states at high temperatures were examined quantum mechanically. In the study, the formation of all gases, with or without carbon, were determined. All the dynamics in which the O2 molecule could be effective in the combustion mechanism and all the elements that could affect the decomposition in the pyrolysis event were determined. The dynamics of the formation and disappearance of the highly stable CO molecule and CH2O (formaldehyde) molecules were shown in detail. It has been shown that the CO molecule is a catalysis that can bond with hydrocarbon groups and decompose them into small hydrocarbon groups at high temperature. In this study, it was shown that high temperature-dependent vibration and rotational energies, CO molecule and H-atom transfers play a role in the decomposition in the pyrolysis system, and the aromatic carbon ring group is the last particle group to decompose. In addition, the formation and dissociation dynamics of sulfoxylic acid, thioformic acid, hydrogen sulfide molecules originating from the Char-S system, as well as the formation conditions of hydrogen cyanide and pyridinyl molecules originating from the Char-N system, were determined. The study also showed that since the N-atom is located in the aromatic carbon ring, it makes the emergence of the nitrous oxide molecule difficult in pyrolysis systems.

A Vanadium Methylidene.

Examples of stable 3d transition metal methylidene complexes are extremely rare. Here we report an isolable and stable vanadium methylidene complex, [(PNP)V(=NAr)(=CH2)] (PNP = N[2-PiPr2-4-methylphenyl]-, Ar = 2,6-iPr2C6H3), via H atom transfer (HAT) from [(PNP)V(NHAr)(CH3)] or [(PNP)V(=NAr)(CH3)] using two or one equivalents of the TEMPO radical (TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl), respectively. Alternatively, the vanadium methylidene moiety can also be formed via the treatment of transient [(PNP)V=NAr] with the Wittig reagent, H2CPPh3. Structural and spectroscopic analysis, including 13C enriched labeling of the methylidene ligand, unequivocally confirmed the terminal nature of a rare 3d methylidene complex, featuring a V=CH2 bond distance of 1.908(2) Å and a highly downfield 13C NMR spectral shift at 298 ppm. In the absence of the ylide, intermediate [(PNP)V=NAr] activates dinitrogen to form an end-on bridging N2 complex, [(PNP)V(=NAr)]2(μ2-η1:η1-N2), having a singlet ground state. Complex [(PNP)V(=NAr)(=CH2)] reacts with H3COTf to form [(PNP)V(=NAr)(OTf)], accompanied by the release of ethylene as evidenced by 1H NMR spectroscopy, and reactivity studies suggest a β-hydride elimination pathway.

Organo-Photocatalytic Anti-Markovnikov Hydroamidation of Alkenes with Sulfonyl Azides: A Combined Experimental and Computational Study.

The construction of C(sp3)-N bonds via direct N-centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo-photocatalytic approach to achieve anti-Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition-metal-free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet-triplet energy transfer manner to achieve photosensitization by the organo-photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4-H bond, which triggers a straightforward H-atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p-toluenethiol could proceed to afford the desired anti-Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

Organo‐Photocatalytic Anti‐Markovnikov Hydroamidation of Alkenes with Sulfonyl Azides: A Combined Experimental and Computational Study

AbstractThe construction of C(sp3)−N bonds via direct N‐centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo‐photocatalytic approach to achieve anti‐Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition‐metal‐free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet‐triplet energy transfer manner to achieve photosensitization by the organo‐photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4−H bond, which triggers a straightforward H‐atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p‐toluenethiol could proceed to afford the desired anti‐Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

Photoredox Catalytic Access to N,O-Acetals from Enamides by Means of Electron-Poor Perylene Bisimides.

N,O-acetals are found as structural motifs in natural products and are important synthetic precursors for N-acylimines as building blocks in organic synthesis for C-C-bond formation and amines. For the synthesis of N,O-acetals, an acid-, base- and metal-free catalytic method is reported applying N,N-di-(2,6-diisopropyl)-1,7-dicyano-perylen-3,4,9,10-tetracarboxylic acid imide and N,N-di-(2,6-diisopropyl)-1,6,7,12-tetrabromo-2,5,8,11-tetracyano-perylen-3,4,9,10-tetracarboxylic acid imide as extremely electron-deficient photocatalysts. The first perylene bisimide highly selectively photocatalyzes the formation of the N,O-acetals as products in high yields, and the second and more electron-deficient perylene bisimide allows these reactions without thiophenol as an H-atom transfer reagent. Calculated electron density maps support this. The reaction scope comprises different substituents at the nitrogen of the enamides and different alcohols as starting material. Dehydroalanines are converted to non-natural amino acids which shows the usefulness of this method for organic and medicinal chemistry.

Integrating Olefin Carboamination and Hofmann-Löffler-Freytag Reaction by Radical Deconstruction of Hydrazonyl N-N Bond.

As a type of elementary organic compounds containing N-N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2-retention and N2-removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2-moiety of hydrazone by a radical facilitated N-N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann-Löffler-Freytag reaction by the reaction of N-homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino-N migration and H-atom transfer. Consequently, a series of structurally significant ϵ-N-sulphonamide-α,α-difluoro-γ-amino acid esters are efficiently produced via continuous C-C bond and dual C-N bonds forging.

Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ.

Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -• ) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BI•) allows for radical-radical coupling to afford the combined crosslink product (BI─BI), which would be oxidized in the presence of O2 -• to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (Cy─BI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct Cy─BI can efficiently inhibit the expression of CHK1, and the irradiation of BI and Cy─BI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.

Shaping the laser control landscape of a hydrogen transfer reaction by vibrational strong coupling. A direct optimal control approach.

Controlling molecular reactivity by shaped laser pulses is a long-standing goal in chemistry. Here, we suggest a direct optimal control approach that combines external pulse optimization with other control parameters arising in the upcoming field of vibro-polaritonic chemistry for enhanced controllability. The direct optimal control approach is characterized by a simultaneous simulation and optimization paradigm, meaning that the equations of motion are discretized and converted into a set of holonomic constraints for a nonlinear optimization problem given by the control functional. Compared with indirect optimal control, this procedure offers great flexibility, such as final time or Hamiltonian parameter optimization. A simultaneous direct optimal control theory will be applied to a model system describing H-atom transfer in a lossy Fabry-Pérot cavity under vibrational strong coupling conditions. Specifically, optimization of the cavity coupling strength and, thus, of the control landscape will be demonstrated.

Computational insights into the zeolite-supported gold nanocluster-catalyzed ethanol dehydrogenation to acetaldehyde.

Zeolite-supported gold nanoclusters play increasingly important roles in heterogeneous catalysis and exhibit unique catalytic properties for ethanol dehydrogenation to acetaldehyde. Nevertheless, the reaction mechanism and potential roles of the zeolite-encapsulated gold nanoclusters during the catalytic process remain unclear. Herein, computational studies were carried out to gain mechanistic insights into ethanol dehydrogenation to acetaldehyde under both aerobic and anaerobic conditions catalyzed by a silicalite-1 zeolite-encapsulated Au3 cluster cation (Au3+-S1). The presence of O2 can significantly promote the ethanol dehydrogenation catalyzed by Au3+-S1. A feasible mechanistic pathway could be initiated via the O2 induced H-atom transfer (HAT) step from the hydrogen of the hydroxyl group to afford ethoxy and OOH radical species. Subsequently, the OOH induced second HAT from α-C-H of the ethoxy intermediate could follow to afford the acetaldehyde product. Moreover, the possible confinement and stabilization effect of the zeolite channels on the ethanol dehydrogenation reaction was discussed.

Photodissociation of deuterated pyrrole-ammonia clusters: H-atom transfer or electron coupled proton transfer?

Several years ago the discovery of a conical intersection offered an explanation for the ultafast photodissociation of pyrrole. Subsequently, the photodissociation of pyrrole ammonia complexes PyH*(NH3)n with n ≥ 3 was studied in the gas phase as a model for a hydrogen-bond forming solvent. Two alternative mechanisms, electron coupled proton transfer (ECPT) and hydrogen atom transfer (HAT, also called the impulsive model, IM), have been proposed. The parent 1 : 1 complex was never studied, due to the short lifetime of the NH4 radical fragment. Here we report experiments on the deuterated species PyD*(ND3)n, including the 1 : 1 complex (n = 1). The velocity distribution of the ND4 radical is well approximated by a Maxwell-Boltzmann distribution of T ≈ 530 K, with a negative anisotropy parameter of β = -0.3. The impulsive model predicts a much narrower velocity distribution with larger negative anisotropy. The ECPT model predicts a long lived intermediate that should allow thermal equilibration of the vibrational energy but should also destroy the rotational memory of the initially excited state. The average kinetic energy agrees with the prediction of the impulsive model, whereas the wide range of kinetic energies is more in line with ECPT. Hence the mechanism seems to be more complex and requires further theoretical modelling.

Kinetic study of the reaction of thiophene-tocopherols with peroxyl radicals enlightenings the role of O˙⋯S noncovalent interactions in H-atom transfer.

Three new α-tocopherol thiophene derivatives were efficiently synthesized, characterized and used for the first time as chain-breaking antioxidants for the inhibition of the autoxidation of reference oxidizable substrates. The rate constant of the reaction with alkylperoxyl (ROO˙) radicals and the stoichiometry of radical trapping (n) for the thiophene-tocopherol compounds were determined by measuring the oxygen consumption during the autoxidation of styrene or isopropylbenzene, using a differential pressure transducer. The measurement of the reaction with ROO˙ radicals in an apolar solvent at 30 °C showed inhibition rate constants (kinh) in the order of 104 M-1 s-1. To rationalise the kinetic results, the effect of the thiophene ring on the H-atom donation by O-H groups of the functionalized tocopherols was investigated by theoretical calculations. The importance of noncovalent interactions (including an unusual O˙⋯S bond) for the stability of the conformers has been shown, and the O-H bond dissociation enthalpy (BDE(OH)) of these derivatives was determined. Finally, the photophysical properties of these new compounds were investigated to understand if the addition of thiophene groups changes the absorption or emission spectra of the tocopherol skeleton for their possible application as luminescent molecular probes.

Competing radical and molecular channels in the unimolecular dissociation of methylformate

The thermal dissociation of methylformate has been characterized by numerous experimental and theoretical studies that all seem to agree that the lowest energetically accessible process is a 3-center H-atom transfer that leads to the molecular products CH3OH + CO. However, these literature studies seem to be at odds with regards to the role of other competing molecular eliminations and bond-fission processes and therefore a complete and resolved mechanistic picture of methylformate thermal dissociation still eludes us. In this work, we have performed high-level electronic structure theory calculations to characterize the energetics of other overlooked molecular and radical processes that can originate on the complex CH3OCHO potential energy surface (PES). The present calculations do indeed confirm that the lowest energy process accessible on this PES is molecular elimination to form CH3OH + CO. However, unlike prior theoretical studies, the present calculations reveal that the second lowest energy process is a 5-center concerted elimination process that leads to the direct formation of H2 + CH2O + CO. We also note that HCO2 from the lowest-lying bond fission has two energetically comparable electronic states (of 2B2 and 2A1 symmetry). Furthermore, the barrier for H-atom migration of CH3OCHO to form the carbene (CH3OCOH) is similar to that for the direct 4-center elimination process leading to CH2O + CH2O characterized in prior literature studies. Radical and molecular pathways to CH3 + HOCO and CH4 + CO2 can also be facilitated from this carbene. Master equation calculations were performed to characterize the competition between the various molecular and radical processes on this more elaborate CH3OCHO PES. The results of the present theoretical analyses were used to resolve outstanding questions on the role of secondary radical-initiated reactions in characterizing prior literature experimental studies.

Interrupted Homolytic Substitution Enables Organoboron Compounds to Inhibit Radical Chain Reactions Rather than Initiate Them.

The reactions of organoboranes with peroxyl radicals are key to their use as radical initiators for a vast array of radical chain reactions, particularly at low temperatures where high stereoselectivity or regioselectivity is desired. Whereas these reactions generally proceed via concerted homolytic substitution (SH2) mechanisms, organoboranes that bear groups that can stabilize tetracoordinate boron radical "ate" complexes (e.g., catecholboranes) undergo this reaction via a stepwise addition/fragmentation sequence and serve as useful stoichiometric alkyl radical precursors. Here we show that arylboronic esters and amides derived from catecholborane and diaminonaphthaleneborane, respectively, are potent radical-trapping antioxidants (RTAs). Mechanistic studies reveal that this is because the radical "ate" complexes derived from peroxyl radical addition to boron are sufficiently persistent to trap another radical in an interrupted SH2 reaction. Remarkably, the reactivity of these organoboranes as inhibitors of autoxidation was shown to translate from simple hydrocarbons to the phospholipids of biological membranes such that they can inhibit ferroptosis, the cell death modality driven by lipid autoxidation and relevant in neurodegeneration and other major pathologies. The unique mechanism of these organoboranes is one of only a handful of RTA mechanisms that are not based on H-atom transfer processes and provide a new dimension to boron chemistry and its applications.

106-fold faster C-H bond hydroxylation by a CoIII,IV2(µ-O)2 complex [via a CoIII2(µ-O)(µ-OH) intermediate] versus its FeIIIFeIV analog.

The hydroxylation of C-H bonds can be carried out by the high-valent CoIII,IV2(µ-O)2 complex 2a supported by the tetradentate tris(2-pyridylmethyl)amine ligand via a CoIII2(µ-O)(µ-OH) intermediate (3a). Complex 3a can be independently generated either by H-atom transfer (HAT) in the reaction of 2a with phenols as the H-atom donor or protonation of its conjugate base, the CoIII2(µ-O)2 complex 1a. Resonance Raman spectra of these three complexes reveal oxygen-isotope-sensitive vibrations at 560 to 590 cm-1 associated with the symmetric Co-O-Co stretching mode of the Co2O2 diamond core. Together with a Co•••Co distance of 2.78(2) Å previously identified for 1a and 2a by Extended X-ray Absorption Fine Structure (EXAFS) analysis, these results provide solid evidence for their "diamond core" structural assignments. The independent generation of 3a allows us to investigate HAT reactions of 2a with phenols in detail, measure the redox potential and pKa of the system, and calculate the O-H bond strength (DO-H) of 3a to shed light on the C-H bond activation reactivity of 2a. Complex 3a is found to be able to transfer its hydroxyl ligand onto the trityl radical to form the hydroxylated product, representing a direct experimental observation of such a reaction by a dinuclear cobalt complex. Surprisingly, reactivity comparisons reveal 2a to be 106-fold more reactive in oxidizing hydrocarbon C-H bonds than corresponding FeIII,IV2(µ-O)2 and MnIII,IV2(µ-O)2 analogs, an unexpected outcome that raises the prospects for using CoIII,IV2(µ-O)2 species to oxidize alkane C-H bonds.