Carbon Radicals Research Articles

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO2 . This visible-light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine- or phosphorus-containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional-group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5-hydrogen atom-transfer process, the rate-limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrII species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2 to generate carboxylates.

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

AbstractRemote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO2. This visible‐light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine‐ or phosphorus‐containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional‐group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5‐hydrogen atom‐transfer process, the rate‐limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrIIspecies generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2to generate carboxylates.

Carbonaceous deposits on aluminide coatings in tritium-producing assemblies

Abstract Co-deposition of carbon atoms with hydrogen isotopes and hydrogenated carbon radicals and molecules is recognized as the main mechanism for tritium retention in the graphite walls of the previous tokamak fusion devices. Significant tritium retention would be a serious concern for safe and economic long-term operation of future fusion test reactors and fusion energy systems. Similar deposits are observed on the surface of the engineered components in a tritium-producing assembly, known as a Tritium-Producing Burnable Absorber Rod (TPBAR). Characterization of the deposits can help understand the tritium transport, accumulation history and distribution in TPBARs. This study reports our recent results from the carbonaceous deposits formed on an aluminide-coated cladding in the lower plenum of a TPBAR following thermal neutron irradiation. The observed deposits are amorphous in nature, consisting of flakes of interconnected nanoscale features. They contain primarily double-bonded carbon (e.g., alkene) and carbonyl carbon, as well as a minor fraction of aliphatic carbon, all of which are likely tritiated. A similar co-deposition process that occurred in previous fusion devices is responsible for the formation and growth of the carbonaceous deposits.

Mass-independent fractionation of titanium isotopes

Forty years ago, the synthesis of ozone has revealed mass-independent fractionation (MIF) of oxygen isotopes. Among the numerous published interpretations of this ozone effect, the present paper reports that a titanium MIF observed during chemical reactions in plasma can be accounted for by one of these theoretical treatments. A gaseous mixture of TiCl 4 /C 5 H 12 carried in a glass tube by a continuous flow of N 2 was submitted to a HF discharge. Carbonaceous grains, presumably resulting from homogeneous condensation, show radial variations in Ti concentration with isotopic variations ranging from −25 to +125% for all m Ti / 48 Ti isotope ratios ( m standing for masses 46, 47, 49 and 50). It is proposed that the reduction rates by carbon radicals, of the metastable molecules formed by the isotope exchange reactions between Ti and TiCl 4 are different if they involve distinguishable or indistinguishable isotopes. A numerical simulation reproduces the experimental isotope patterns defined by the m Ti / 48 Ti isotope ratios.

Radical Dehydroxylative Alkylation of Tertiary Alcohols by Ti Catalysis.

Deoxygenative radical C-C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10-g-scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C-OH bond.

A Mitochondrion-Localized Two-Photon Photosensitizer Generating Carbon Radicals Against Hypoxic Tumors.

The efficacy of photodynamic therapy is typically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen-independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as a mitochondrion-localized carbon-radical initiator. Its emission is turned on under hypoxic conditions after reduction by reductase. Furthermore, its two-photon excitation properties (λex =730 nm) are highly desirable for imaging. Upon irradiation, the reduced form of the complex generates carbon radicals, leading to a loss of mitochondrial membrane potential and cell death (IC50light =2.1 μm, IC50dark =58.2 μm, PI=27.7). The efficacy of the complex as a PDT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge, it is the first metal-complex-based theranostic agent which can generate carbon radicals for oxygen-independent two-photon photodynamic therapy.

Size and stability modulation of Pd nanoparticles on porous hypercrosslinked ionic polymer for heterogeneous aerobic oxidative coupling of diaryl ether

Oxidative coupling of two aromatic CH bonds is normally catalyzed by Pd(II) species involving an electrophilic attacking step. Herein, we demonstrated surprisingly the high activity of heterogeneous Pd(0) nanoparticles (NPs) in catalyzing the intramolecular oxidative coupling of diaryl ether with O2. The Pd(0) NPs with different average particle sizes were constructed by using the supports of ionic hypercrosslinked porous polymers that were straightforwardly synthesized through the copolymerization of 2,3-pyridinedicarboxylic anhydride and biphenyl in a chlorosulfonic acid-catalyzed route. In the case of moderate ionic moiety content, the constructed Pd(0) NPs were highly active in the coupling of diphenylether to dibenzofuran, affording a high yield of 72 % associated with a large turnover number of 91 that exceeded 18-folds of homogeneous palladium acetate. Kinetic analysis and radical quenching results demonstrate a carbon radical related catalytic pathway. Following the same methodology, various other diaryl ether with electro-donating and electro-withdrawing groups were converted into the corresponding dibenzofuran derivatives.

Re-Examination of Some Carbocations. Structures, Energies, and Charge Distributions.

Chemists have had a long-standing interest in reactive intermediates such as carbenes, carbon radicals, carbanions, and carbocations. Carbocations are an interesting part of this group because of their tendency to undergo rearrangement, sometimes forming bridged ions, as well as their ability in many cases of spreading out the positive charge over several atoms. We have re-examined some of these cases using high-level compound procedures, W1BD and G4, as well as by considering the charge distributions making use of the Hirshfeld method that has been shown to uniquely correlate with several types of experimental data.

Electrocatalytic Deuteration of Halides with D2 O as the Deuterium Source over a Copper Nanowire Arrays Cathode.

Precise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D2 O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross-coupling of carbon and deuterium free radicals might be involved for this ipso-selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C-H to C-D transformations were achieved with high yields and deuterium ratios through a one-pot halogenation-deuterodehalogenation process. Efficient deuteration of less-active bromide substrates, specific deuterium incorporation into top-selling pharmaceuticals, and oxidant-free paired anodic synthesis of high-value chemicals with low energy input highlighted the potential practicality.

Electrocatalytic Deuteration of Halides with D2O as the Deuterium Source over a Copper Nanowire Arrays Cathode

AbstractPrecise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D2O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross‐coupling of carbon and deuterium free radicals might be involved for this ipso‐selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C−H to C−D transformations were achieved with high yields and deuterium ratios through a one‐pot halogenation–deuterodehalogenation process. Efficient deuteration of less‐active bromide substrates, specific deuterium incorporation into top‐selling pharmaceuticals, and oxidant‐free paired anodic synthesis of high‐value chemicals with low energy input highlighted the potential practicality.

Silicon\u2013silicon \u03c0 single bond

A carbon–carbon double bond consists of a σ bond and a π bond. Recently, the concept of a π single bond, where a π bond is not accompanied by a σ bond, has been proposed in diradicals containing carbon and heteroatom radical centers. Here we report a closed-shell compound having a silicon–silicon π single bond. 1,2,2,3,4,4-Hexa-tert-butylbicyclo[1.1.0]tetrasilane has a silicon−silicon π single bond between the bridgehead silicon atoms. The X-ray crystallographic analysis shows that the silicon−silicon π single bond (2.853(1) Å) is far longer than the longest silicon−silicon bond so far reported. In spite of this unusually long bond length, the electrons of the 3p orbitals are paired, which is confirmed by measurement of electron paramagnetic resonance, and magnetic susceptibility and natural bond orbital analysis. The properties of the silicon−silicon π single bond are studied by UV/Vis and 29Si NMR spectroscopy, and theoretical calculations.

Total Synthesis of Diospyrodin and Its Three Diastereomers.

Antibacterial diospyrodin (1) was synthesized in 13 steps. Et3B and O2 promoted the formation of an α-alkoxy carbon radical from l-ribose-derived α-alkoxyacyl telluride 5, which reacted with d-glucose-derived aldehyde 4. The radical addition realized the convergent assembly of the contiguously hydroxylated carbon-chain of 3-α and greatly contributed to streamlining the synthetic route. Compound 3-α was transformed not only to 1 but also to its three diastereomers by functional group manipulations.

An Atomistic Study of the Stress Corrosion Cracking in Graphene.

Using molecular dynamics (MD) simulations, we study the mechanism of stress corrosion cracking in graphene. Two sets of modelings are conducted. In the first one, large graphene sheets with cracks in the armchair and zigzag directions are exposed to oxygen molecules. The crack growth as a result of chemical reactions between carbon radicals and oxygen molecules at different mechanical tensile stress levels is studied. In the second set of simulations, MD simulations are combined with the density functional-based tight bonding method to enhance the accuracy. This set of modelings focuses on a smaller zone in the vicinity of the crack tip. The impact of initial crack orientation on corrosion is studied by investigating corrosion of cracks in both armchair and zigzag directions. We investigate the subcritical crack propagation occurring as a result of the combined effects of both mechanical loading and chemical reactions. Our results show that cracks in graphene can grow due to chemical reactions with the environmental molecules. The MD modelings also predict that reaction of carbon atoms with oxygen molecules might lead to a stress relaxation at the crack tip, hence preventing further crack propagation. The results show that subcritical crack growth can happen by two mechanisms, which include the failure of C-C bonds or by removing the carbon atoms from graphene sheets in the form of CO or CO2 molecules.

Mechanism study on photo-oxidation dehydrogenation of cyclometalated Ir(III) amino acid complexes

Aerobic oxidation of amino acid complexes is an important process for the functionalization of amino acids. However, the reaction mechanism is still uncertain. Two enantiopure imino acid complexes Δ-[Ir(pq)2(ala-2H)] and Δ-[Ir(ppy)2(ala-2H)] (where pq is 2-phenylquinoline, ppy is 2-phenylpyridine and ala is alanine) have been synthesized respectively via the dehydrogenated oxidation reaction of the corresponding amino acid complexes Δ-[Ir(pq)2(l-ala)] and Δ-[Ir(ppy)2(l-ala)] in EtOH using visible light as the driving force and oxygen as an oxidant under mild conditions. The imino acid complexes have been fully characterized by NMR and MS techniques as well as X-ray single-crystal determination. The mechanism studies show singlet oxygen (1O2) is the main reactive oxygen species (ROS) and the carbon radical intermediate may involve in the reaction process. Therefore, a reaction mechanism involving the formation of a ligand-radical intermediate rather than the higher oxidation state of the metal center was proposed.

Reversible Formation of Alkyl Radicals at [Fe4S4] Clusters and Its Implications for Selectivity in Radical SAM Enzymes.

All kingdoms of life use the transient 5'-deoxyadenosyl radical (5'-dAdo•) to initiate a wide range of difficult chemical reactions. Because of its high reactivity, the 5'-dAdo• must be generated in a controlled manner to abstract a specific H atom and avoid unproductive reactions. In radical S-adenosylmethionine (SAM) enzymes, the 5'-dAdo• is formed upon reduction of SAM by an [Fe4S4] cluster. An organometallic precursor featuring an Fe-C bond between the [Fe4S4] cluster and the 5'-dAdo group was recently characterized and shown to be competent for substrate radical generation, presumably via Fe-C bond homolysis. Such reactivity is without precedent for Fe-S clusters. Here, we show that synthetic [Fe4S4]-alkyl clusters undergo Fe-C bond homolysis when the alkylated Fe site has a suitable coordination number, thereby providing support for the intermediacy of organometallic species in radical SAM enzymes. Addition of pyridine donors to [(IMes)3Fe4S4-R]+ clusters (R = alkyl or benzyl; IMes = 1,3-dimesitylimidazol-2-ylidene) generates R•, ultimately forming R-R coupled hydrocarbons. This process is facile at room temperature and allows for the generation of highly reactive radicals including primary carbon radicals. Mechanistic studies, including use of the 5-hexenyl radical clock, demonstrate that Fe-C bond homolysis occurs reversibly. Using these experimental insights and kinetic simulations, we evaluate the circumstances in which an organometallic intermediate can direct the 5'-dAdo• toward productive H-atom abstraction. Our findings demonstrate that reversible homolysis of even weak M-C bonds is a feasible protective mechanism for the 5'-dAdo• that can allow selective X-H bond activation in both radical SAM and adenosylcobalamin enzymes.

Dose rate effects on shape memory epoxy resin during 1 MeV electron irradiation in air

The effects of 1 MeV electron irradiation in air at a fixed accumulated dose and dose rates of 393.8, 196.9, 78.8, and 39.4 Gy s−1 on a shape memory epoxy (SMEP) resin were studied. Under low-dose-rate irradiation, accelerated degradation of the shape memory performance was observed; specifically, the shape recovery ratio decreased exponentially with increasing irradiation time (that is, with decreasing dose rate). In addition, the glass transition temperature of the SMEP, as measured by dynamic mechanical analysis, decreased overall with decreasing dose rate. The dose rate effects of 1 MeV electron irradiation on the SMEP were confirmed by structural analysis using electron paramagnetic resonance (EPR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The EPR spectra showed that the concentration of free radicals increased exponentially with increasing irradiation time. Moreover, the FTIR spectra showed higher intensities of the peaks at 1660 and 1720 cm-1, which are attributed to stretching vibrations of amide CO and ketone/acid CO, at lower dose rates. The intensities of the IR peaks at 1660 and 1720 cm-1 increased exponentially with increasing irradiation time, and the relative intensity of the IR peak at 2926 cm-1 decreased exponentially with increasing irradiation time. The solid-state 13C nuclear magnetic resonance (NMR) spectra of the SMEP before and after 1 MeV electron irradiation at a dose of 1970 kGy and a dose rate of 78.8 Gy s-1 indicated damage to the CH2–N groups and aliphatic isopropanol segment. This result is consistent with the detection of nitrogenous free radicals, a phenoxy-type free radical, and several types of pyrolytic carbon radicals by EPR. During the subsequent propagation process, the free radicals produced at lower dose rates were more likely to react with oxygen, which was present at higher concentrations, and form the more destructive peroxy free radicals and oxidation products such as acids, amides, and ketones. The increase in peroxy free radicals at lower dose rates was thought to accelerate the degradation of the macroscopic performance of the SMEP.

Enantioselective, Aerobic Copper-Catalyzed Intramolecular Carboamination and Carboetherification of Unactivated Alkenes.

Reduction of waste is an important goal of modern organic synthesis. We report herein oxidase reactivity for enantioselective intramolecular copper-catalyzed alkene carboamination and carboetherification reactions where previously used stoichiometric MnO2 has been replaced with oxygen. This substitution was risky as the reaction mechanism is thought to involve C-C bond formation via addition of alkyl carbon radicals to arenes. Such intermediates are also susceptible to C-O bond formation via O2 addition. Control of absolute stereochemistry under aerobic conditions was also uncertain. The oxidative cyclization efficiencies appear to track with the ease of the radical addition to the arenes.

Radical-Mediated Strategies for the Functionalization of Alkenes with Diazo Compounds.

One of the most common reactions of diazo compounds with alkenes is cyclopropanation, which occurs through metal carbene or free carbene intermediates. Alternative functionalization of alkenes with diazo compounds is limited, and a methodology for the addition of the elements of Z-CHR2 (with Z = H or heteroatom, and CHR2 originates from N2═CR2) across a carbon-carbon double bond has not been reported. Here we report a novel reaction of diazo compounds utilizing a radical-mediated addition strategy to achieve difunctionalization of diverse alkenes. Diazo compounds are transformed to carbon radicals with a photocatalyst or an iron catalyst through PCET processes. The carbon radical selectively adds to diverse alkenes, delivering new carbon radical species, and then forms products through hydroalkylation by thiol-assisted hydrogen atom transfer (HAT), or forms azidoalkylation products through an iron catalytic cycle. These two processes are highly complementary, proceed under mild reaction conditions, and show high functional group tolerance. Furthermore, both transformations are successfully performed on a gram-scale, and diverse γ-amino esters, γ-amino alcohols, and complex spirolactams are easily prepared with commercially available reagents. Mechanistic studies reveal the plausible pathways that link the two processes and explain the unique advantages of each.

Scalable Photoelectrochemical Dehydrogenative Cross‐Coupling of Heteroarenes with Aliphatic C−H Bonds

Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross-coupling of heteroarenes with aliphatic C-H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross-coupling of heteroarenes and C(sp3 )-H donors through H2 evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp3 )-H donor is converted to a nucleophilic carbon radical through H-atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl2 from Cl- . The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.

Scalable Photoelectrochemical Dehydrogenative Cross‐Coupling of Heteroarenes with Aliphatic C−H Bonds

AbstractHeteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross‐coupling of heteroarenes with aliphatic C−H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross‐coupling of heteroarenes and C(sp3)−H donors through H2 evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp3)−H donor is converted to a nucleophilic carbon radical through H‐atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl2 from Cl−. The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.