Hydrogen Atom Transfer Process Research Articles

Cobalt‐Catalyzed Chemoselective Isomerization of 2‐Substituted Allyl Ethers Induced by Hydrogen Atom Transfer

AbstractA simple, mild and efficient method for the isomerization of 2‐substituted allyl ethers has been developed by cobalt‐catalyzed hydrogen atom transfer (HAT) process. The trivalent cobalt complex oxidized in‐situ by tert‐butyl hydroperoxide (tBuOOH) exhibits higher catalytic activity than prefabricated trivalent cobalt catalysts. This facile protocol displays excellent chemoselectivity, good functional group tolerance and high yields. The obtained vinyl ethers can be easily hydrolyzed by N‐iodosuccinimide/water to afford corresponding phenols or alcohols.

Visible‐light‐driven α‐Oxidation of Amide C(sp3)−H Bonds to Imides via N‐Bromosuccinimide and Water

AbstractAn efficient, metal‐free oxidation method of the N‐ortho C(sp3)−H bond of amide via visible‐light irradiation has been developed. A broad range of imides can be facilely obtained at room temperature and this protocol is showcased in the gram‐scale synthesis. Preliminary mechanistic studies revealed that a hydrogen atom transfer (HAT) process was involved and H2O offered the main oxygen source to achieve greener photochemical C(sp3)−H oxidation.

Electrocatalytic Generation of Acyl Radicals and Their Applications

AbstractIn this review, we highlighted the main achievements in the field of electrocatalytic generation of acyl radicals and their applications. These electrochemical strategies were introduced with an emphasis on the substrate scope, reaction limitation and underlying mechanism. The related reactions were categorized according to the pathways of acyl radical generation, including outer‐sphere electron transfer (ET), inner‐sphere ET, and hydrogen atom transfer (HAT) processes.

Membrane-based TBADT recovery as a strategy to increase the sustainability of continuous-flow photocatalytic HAT transformations

Photocatalytic hydrogen atom transfer (HAT) processes have been the object of numerous studies showcasing the potential of the homogeneous photocatalyst tetrabutylammonium decatungstate (TBADT) for the functionalization of C(sp3)–H bonds. However, to translate these studies into large-scale industrial processes, careful considerations of catalyst loading, cost, and removal are required. This work presents organic solvent nanofiltration (OSN) as an answer to reduce TBADT consumption, increase its turnover number and lower its concentration in the product solution, thus enabling large-scale photocatalytic HAT-based transformations. The operating parameters for a suitable membrane for TBADT recovery in acetonitrile were optimized. Continuous photocatalytic C(sp3)-H alkylation and amination reactions were carried out with in-line TBADT recovery via two OSN steps. Promisingly, the observed product yields for the reactions with in-line catalyst recycling are comparable to those of reactions performed with pristine TBADT, therefore highlighting that not only catalyst recovery (>99%, TON > 8400) is a possibility, but also that it does not happen at the expense of reaction performance.

Low-Temperature C-H Bond Activation via Photocatalysis: Highly Efficient Ethylbenzene Dehydrogenation into Styrene on Rutile TiO2(110).

The direct dehydrogenation of hydrocarbons to olefins under mild conditions is an atom-economical but challenging route. Here, we have investigated photocatalytic ethylbenzene dehydrogenation into styrene on rutile(R)-TiO2(110) using the temperature-programmed desorption (TPD) method. The results demonstrate that photocatalytic ethylbenzene dehydrogenation into styrene occurs on R-TiO2(110) in a stepwise manner, in which the initial α-C-H bond cleavage occurs facilely under UV irradiation via a possible homolytic hydrogen atom transfer process and then is followed by the second C-H bond cleavage induced by either photocatalysis at ∼120 K or thermocatalysis at >400 K. With preadsorbed oxygen atoms to eliminate hydrogen atoms from ethylbenzene dehydrogenation and excess electrons on the surface, the yield of styrene is largely enhanced by about 4 times. The results not only demonstrate a photocatalytic route for ethylbenzene dehydrogenation into styrene on R-TiO2(110) but also advance our understanding of the photocatalytic activation of the saturated C-H bond with TiO2.

Enantioselective Radical Trifluoromethylation of Benzylic C-H Bonds via Cooperative Photoredox and Copper Catalysis.

The first enantioselective radical trifluoromethylation of benzylic C-H bonds has been established by a cooperative photoredox and copper catalysis system, providing straightforward access to structurally diverse benzylic trifluoromethylation products in good yields with excellent enantioselectivities under mild conditions. Our method features a broad substrate scope and excellent functional group compatibility. Merging the cooperative photoredox catalysis with copper catalysis is essential for the reaction, where the photoredox catalysis is used for the generation of benzylic radicals from alkyl arenes through a hydrogen atom transfer process and the copper catalysis is used for the enantioselective trifluoromethylation of the benzylic radicals.

Striking Size and Doping Effects of Ti-Si-O Clusters on Methane Conversion Reactions.

The size and doping effects in methane activation by Ti-Si-O clusters have been explored by using a combination of gas-phase experiments and quantum chemical calculations. All [Tim Sin O2(m+n) ].+ (m+n=2, 3, 8, 10, 12, 14) clusters can extract a hydrogen from methane. The associated energies and structures have been revealed in detail. Moreover, the doping and size effects have been discussed involving generalized Kohn-Sham energy decomposition analysis, natural population analysis, Wiberg bond indexes (WBI), molecular polarity index (MPI) and ionization potential (IP). It suggested that Ti-Si-O clusters with a low Ti : Si ratio is beneficial to adsorbing methane and inclination to the hydrogen atom transfer (HAT) process, while the clusters with a high Ti : Si ratio favors the generation of a terminal oxygen radical and results in high reactivity and turnover frequency. On the other hand, a cluster size of m+n=12 is recommended considering both the ionization potential and the turnover frequency of the reaction. Hopefully, these finding will be instructive for the design of high-performance Ti-Si-O catalyst toward methane conversion.

Anthraquinone-Based Metal-Organic Frameworks as a Bifunctional Photocatalyst for C-H Activation.

Metal-organic frameworks (MOFs) have gained attention as multifunctional catalytic platforms, allowing us to gain important insights into synergistically activating both C-H bonds and oxygen for improving oxidation. Herein, by ingenious incorporation of anthraquinone, we report an anthraquinone-based MOF as a bifunctional heterogeneous photocatalytic platform to simultaneously activate inert C(sp3)-H bonds and oxygen for C-H bond oxidation. Making use of the rigid framework with the fixation and isolation effect, both a great chemical stability and bifunctional synergistic photocatalytic effects were obtained through the immobilization of anthraquinone into a MOF. Importantly, while decorating two carboxyl groups on anthraquinone, the carbonyl groups of anthraquinone photosensitizers were not involved in coordinating the self-assembly and orderly arranged on the wall of channels that were constructed through a π-π interaction between the anthraquinone moieties in the adjacent layers, which was beneficial to form and stabilize the excited-state radical intermediates in the molecule-fenced channels, and the close proximity between the catalytic sites and the substrates to abstract a hydrogen atom from the substrate through the hydrogen atom transfer process aimed at activating the inertness of C-H bonds. Moreover, high-density-distributed anthraquinone dyes in the confined channels would activate oxygen to form singlet oxygen (1O2) through an energy transfer pathway, further promoting inert C(sp3)-H bond oxidation efficiency. Under visible light irradiation, this anthraquinone-based MOF was successfully applied to explore activation and oxidation of a series of substrates containing benzylic C(sp3)-H bonds in the presence of air or oxygen to produce the corresponding carbonyl products. This bifunctional photocatalytic platform based on a heterogeneous MOF provides an available catalytic avenue to develop a scalable and sustainable synthetic strategy using green and sustainable oxygen as the potent oxidant.

Photo-Induced Ruthenium-Catalyzed Double Remote C(sp2 )-H / C(sp3 )-H Functionalizations by Radical Relay.

Distal C(sp2)−H and C(sp3)−H functionalizations have recently emerged as step‐economical tools for molecular synthesis. However, while the C(sp2)−C(sp3) construction is of fundamental importance, its formation through double remote C(sp2)−H/C(sp3)−H activation has proven elusive. By merging the ruthenium‐catalyzed meta‐C(sp2)−H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp2)−H/C(sp3)−H functionalizations via photo‐induced ruthenium‐mediated radical relay. Thus, meta‐C(sp2)−H arene bonds and remote C(sp3)−H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light—notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho‐C−H activation, single‐electron‐transfer (SET), 1,n‐HAT (n=5–7) and σ‐activation by means of a single ruthenium(II) catalyst.

New Role for Photoexcited Na2 Eosin Y via the Direct Hydrogen Atom Transfer Process in Photochemical Visible-Light-Induced Synthesis of 2-Amino-4H-Chromene Scaffolds Under Air Atmosphere.

The Knoevenagel–Michael cyclocondensation of malononitrile, aryl aldehydes, and resorcinol was used as a multicomponent green tandem strategy for the metal-free synthesis of 2-amino-4H-chromene scaffolds. Through a visible-light-induced process, the photo-excited state functions derived from Na2 eosin Y were used as direct hydrogen atom transfer catalysts in aqueous ethanol at ambient temperature. The purpose of this study was to examine the further use of an organic dye that does not contain metal and is inexpensive and commercially available. Na2 eosin Y is synthesized by photochemical means using the least amount of catalyst, which results in excellent yields, energy efficiency, and environmental friendliness, high atom economy, time-saving features, and ease of operation. As a result, some properties of green and sustainable chemistry are met. This kind of cyclization can be performed on a gram scale, indicating the potential utility of this reaction in industry.

Electrochemical C(sp3)-H Functionalization of γ-Lactams Based on Hydrogen Atom Transfer.

We describe the electrochemical α-amidoalkylation of γ-lactams based on transition-metal-free cross-coupling via hydrogen atom transfer. The highly selective hydrogen atom transfer process allows for a broad substrate scope including both inter- and intramolecular reactions. Also, the construction of quaternary centers was realized by a double hydrogen atom transfer protocol to afford spirocycles. Detailed mechanistic studies including experimental and computational studies are provided to support the reaction pathway.

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.

A mechanistic switch in C−H bond activation by elusive FeV(O)(TAML) reaction intermediate: A theoretical study

The divergent behavior of C−H bond oxidations of aliphatic substrates compared to those of aromatic substrates shown in Gupta's experiment was mechanistically studied herein by means of density functional theory calculations. Our calculations reveal that such difference is caused by different reaction mechanisms between two kinds of substrates (the aliphatic cyclohexane, 2,3-dimethylbutane and the aromatic toluene, ethylbenzene and cumene). For the aliphatic substrates, C−H oxidation by the oxidant FeV(O)(TAML) is a hydrogen atom transfer process; whereas for the aromatic substrates, C−H oxidation is a proton-coupled electron transfer (PCET) process with a proton transfer character on the transition state, that is, a proton-coupled electron transfer process holding a proton transfer-like transition state (PCET(PT)). This difference is caused by the strong π−π interactions between the tetra-anionic TAML ring and the phenyl ring of the aromatic substrates, which has a “pull” effect to make the electron transfer from substrates to the Fe=O moiety inefficient.

Identification of a Self-Photosensitizing Hydrogen Atom Transfer Organocatalyst System.

We developed organocatalyst systems to promote the cleavage of stable C-H bonds, such as formyl, α-hydroxy, and benzylic C-H bonds, through a hydrogen atom transfer (HAT) process without the use of exogenous photosensitizers. An electronically tuned thiophosphoric acid, 7,7'-OMe-TPA, was assembled with substrate or co-catalyst N-heteroaromatics through hydrogen bonding and π-π interactions to form electron donor-acceptor (EDA) complexes. Photoirradiation of the EDA complex induced stepwise, sequential single-electron transfer (SET) processes to generate a HAT-active thiyl radical. The first SET was from the electron-rich naphthyl group of 7,7'-OMe-TPA to the protonated N-heteroaromatics and the second proton-coupled SET (PCET) from the thiophosphoric acid moiety of 7,7'-OMe-TPA to the resulting naphthyl radical cation. Spectroscopic studies and theoretical calculations characterized the stepwise SET process mediated by short-lived intermediates. This organocatalytic HAT system was applied to four different carbon-hydrogen (C-H) functionalization reactions, hydroxyalkylation and alkylation of N-heteroaromatics, acceptorless dehydrogenation of alcohols, and benzylation of imines, with high functional group tolerance.

Mechanistic study on the radical scavenging activity of viniferins

As an important chemical component of grapes, viniferins are essential dimers of natural product resveratrol with good antioxidant activity. In this study, we have examined the antioxidant activity of two viniferin molecules (δ-viniferin and ε-viniferin) with ·OH/·OOH radicals. Density functional theory (DFT) calculations at the M062X/6–311++G(d,p)-SMD//M062X/6–311G(d,p) level of theory in the gas phase, water, and benzene used to examine two crucial radical scavenging pathways: hydrogen atom transfer (HAT) and the radical adduct formation (RAF). Then, the radical scavenging activities of the two molecules are compared kinetically and thermodynamically. The Gibbs free energy of activation (ΔG≠) and rate constant (kTST) are calculated using the conventional transition state theory (TST), and the results reveal that HAT and RAF processes compete in different solvents. Furthermore, molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) of both the compounds are computed to elucidate their antioxidant activity. The results show that the RAF site appears at the >C7C8< double bond position of δ- and ε-viniferins, and the most favorable HAT positions of δ-viniferin and ε-viniferin are 12′-OH and 12-OH, respectively; in addition, ε-viniferin is a more potent radical scavenging agent than δ-viniferin. These findings provide useful insights on the antioxidant activity of viniferins and different radical scavenging mechanisms of antioxidants, which can be beneficial for improving the practical utilization of resveratrol dimer and other analogs.

Iron-Catalyzed Photoredox Functionalization of Methane and Heavier Gaseous Alkanes: Scope, Kinetics, and Computational Studies.

Herein, we report the development of the photocatalytic C-H functionalization of methane, ethane, and heavier gaseous alkanes with good yields and selectivity, broad scope (57 examples), mild conditions, and low cost. Kinetics and density functional theory calculations were investigated for the key photoinduced ligand-to-metal charge transfer and hydrogen atom transfer processes to reveal the detailed mechanism of iron photocatalysis. This work may bring novel ideas for feedstock upgrading and catalyst design.

Photocatalyzed site-selective C(sp3)-H sulfonylation of toluene derivatives and cycloalkanes with inorganic sulfinates

The development of practical methods for the direct and selective C(sp3)-H functionalization of hydrocarbons is an attractive topic in synthetic chemistry. Although the radical-mediated hydrogen atom transfer (HAT) process has shown considerable potential in such reactions, it still faces fundamental problems associated with reactivity and selectivity. Herein, we report a convenient and economic approach to site-selective C(sp3)-H sulfonylation via photo-induced HAT catalysis. Employing a conjugated polycyclic quinone as a direct HAT photocatalyst, commercially available inorganic sulfinates as the sulfonylation source, copper triflate as an inexpensive oxidant, a variety of toluene derivatives and cycloalkanes were converted into biologically and synthetically interesting sulfone products under mild conditions. The mechanistic studies reveal that the reaction sequence involves direct HAT-induced radical formation and a subsequent copper-mediated organometallic process for the C-S bond formation. This method offers an appealing opportunity to furnish high value-added products from abundant hydrocarbon starting materials and inexpensive reagents.

Radical Carbonyl Umpolung Arylation via Dual Nickel Catalysis.

The formation of carbon-carbon bonds lies at the heart of synthetic organic chemistry and is widely applied to construct complex drugs, polymers, and materials. Despite its importance, catalytic carbonyl arylation remains comparatively underdeveloped, due to limited scope and functional group tolerance. Herein we disclose an umpolung strategy to achieve radical carbonyl arylation via dual catalysis. This redox-neutral approach provides a complementary method to construct Grignard-type products from (hetero)aryl bromides and aliphatic aldehydes, without the need for pre-functionalization. A sequential activation, hydrogen-atom transfer, and halogen atom transfer process could directly convert aldehydes to the corresponding ketyl-type radicals, which further react with aryl-nickel intermediates in an overall polarity-reversal process. This radical strategy tolerates─among others─acidic functional groups, heteroaryl motifs, and sterically hindered substrates and has been applied in the late-stage modification of drugs and natural products.

Vanadium(VIV)–Porphyrin-Based Metal–Organic Frameworks for Synergistic Bimetallic Activation of Inert C(sp3)–H Bonds

Activation and selective functionalization of inert C(sp3)-H bonds remain one of the most challenging tasks in current synthetic chemistry. Herein, by decorating vanadium(VIV)-porphyrin into metal-organic frameworks (MOFs) to stabilize the active tertbutyl peroxide radical, we reported a new approach to accomplish inert C(sp3)-H bond activation by a synergistic bimetallic strategy via a hydrogen atom transfer process under mild conditions. The stabilized peroxide radical by VIV-porphyrin-based MOFs abstracted a hydrogen atom from the inert C(sp3)-H bonds for direct oxidization transformation utilizing environmentally friendly oxygen. Taking advantage of the high stability of Zr6 clusters, the new Zr-MOF was recyclable six times without a conversion efficiency decrease. From this foundation, {Mn3(μ3-O)} cluster nodes with potential unsaturated coordinated sites were introduced into MOFs to replace Zr6 clusters, realizing the pre-activation of substrates through the interaction between Mn nodes and substrates. The synergistic bimetallic activation effect of VIV-porphyrin and Mn nodes dramatically promoted the conversion efficiency and product selectivity for inert C(sp3)-H bond functionalization.

Understanding Hydrogen Atom and Hydride Transfer Processes during Electrochemical Alcohol and Aldehyde Oxidation

Selective oxidation of alcohols and aldehydes to their corresponding carboxylic acids is of broad importance for applications in organic synthesis. These reactions can be performed at the anode of electrochemical and photoelectrochemical cells that produce fuels at the cathode (e.g., water reduction to form H2), allowing for the production of valuable products at both electrodes. NiOOH is among the most promising electrocatalysts for selectively converting alcohols and aldehydes to carboxylic acids. Recent work has revealed that electrochemical alcohol and aldehyde oxidation can occur through two different pathways, one via hydrogen atom transfer and the other via hydride transfer; however, details of these mechanisms are yet to be elucidated. In this work, we examined the effect of pH and the concentration of aliphatic and aromatic alcohols and aldehydes to determine the key factors and steps that affect the kinetics of the two oxidation pathways. Through these experiments, we obtained a comprehensive mechanistic understanding of the two pathways. These results were complemented by kinetic isotope effect experiments to further probe which steps control the rate of each pathway. We then used the understanding these experiments enabled, coupled with computational results, to propose that the ability of alcohols and aldehydes to outcompete OH– for adsorption on Ni4+ sites is a key predictor of which oxidation pathway will be favored.