Hydrogen Abstraction Research Articles

Harnessing the potential of acyl triazoles in bifunctional cobalt-catalyzed radical cross-coupling reactions

Persistent radicals facilitate numerous selective radical coupling reactions. Here, we have identified acyl triazole as a new and versatile moiety for generating persistent radical intermediates through single-electron transfer processes. The efficient generation of these persistent radicals is facilitated by the formation of substrate-coordinated cobalt complexes, which subsequently engage in radical cross-coupling reactions. Remarkably, triazole-coordinated cobalt complexes exhibit metal-hydride hydrogen atom transfer (MHAT) capabilities with alkenes, enabling the efficient synthesis of diverse ketone products without the need for external ligands. By leveraging the persistent radical effect, this catalytic approach also allows for the development of other radical cross-coupling reactions with two representative radical precursors. The discovery of acyl triazoles as effective substrates for generating persistent radicals and as ligands for cobalt catalysis, combined with the bifunctional nature of the cobalt catalytic system, opens up new avenues for the design and development of efficient and sustainable organic transformations.

Zwitterionic Acridinium Amidate: A Nitrogen‐Centered Radical Catalyst for Photoinduced Direct Hydrogen Atom Transfer

AbstractThe development of small organic molecules that can convert light energy into chemical energy to directly promote molecular transformation is of fundamental importance in chemical science. Herein, we report a zwitterionic acridinium amidate as a catalyst for the direct functionalization of aliphatic C−H bonds. This organic zwitterion absorbs visible light to generate the corresponding amidyl radical in the form of excited‐state triplet diradical with prominent reactivity for hydrogen atom transfer to facilitate C−H alkylation with a high turnover number. The experimental and theoretical investigations revealed that the noncovalent interactions between the anionic amidate nitrogen and a pertinent hydrogen‐bond donor, such as hexafluoroisopropanol, are crucial for ensuring the efficient generation of catalytically active species, thereby fully eliciting the distinct reactivity of the acridinium amidate as a photoinduced direct hydrogen atom transfer catalyst.

Zwitterionic Acridinium Amidate: A Nitrogen-Centered Radical Catalyst for Photoinduced Direct Hydrogen Atom Transfer.

The development of small organic molecules that can convert light energy into chemical energy to directly promote molecular transformation is of fundamental importance in chemical science. Herein, we report a zwitterionic acridinium amidate as a catalyst for the direct functionalization of aliphatic C-H bonds. This organic zwitterion absorbs visible light to generate the corresponding amidyl radical in the form of excited-state triplet diradical with prominent reactivity for hydrogen atom transfer to facilitate C-H alkylation with a high turnover number. The experimental and theoretical investigations revealed that the noncovalent interactions between the anionic amidate nitrogen and a pertinent hydrogen-bond donor, such as hexafluoroisopropanol, are crucial for ensuring the efficient generation of catalytically active species, thereby fully eliciting the distinct reactivity of the acridinium amidate as a photoinduced direct hydrogen atom transfer catalyst.

Triphasic Hydroxysilylation of Alkenes by Mechanically Piezoelectric Catalysis.

The 1,2-hydroxysilylation of alkenes is crucial for synthesizing organosilicon compounds which are key intermediates in material science, pharmaceuticals, and organic synthesis. The development of strategies employing hydrogen atom transfer pathways is currently hindered by the existence of various competing reactions. Herein, we reported a novel mechanochemical strategy for the triphasic 1,2-hydroxysilylation of alkenes through a single-electron-transfer pathway. Our approach not only circumvents competitive reactions to enable the first-ever 1,2-hydroxysilylation of unactivated alkenes but also pioneers the research in mechanic force-induced triphasic reactions under ambient conditions. This gentle method offers excellent compatibility with various functional groups, operates under simple and solvent-free conditions, ensures rapid reaction time. Preliminary mechanistic investigations suggest that silylboronate can be transformed to a silicon radical by highly polarized Li2TiO3 particles and oxygen under ball-milling condition.

Biocatalytic Carbenoid N-H Insertions Via Engineered Myoglobins: A Systematic Reaction Mechanism Study

Recently engineered myoglobins have demonstrated excellent biocatalytic activities for a broad range of carbenoid N-H insertion reactions with up to >99% yield. Such biocatalysts offer various tuning points beyond protein residues, such as metal center, and axial ligand, to regulate different chemical reactivities. However, there is no computational mechanistic study to reveal its basic reaction mechanism, which could be utilized to study effects of different catalyst component for rational biocatalyst design. The reported computational mechanistic papers of other heme protein catalyzed N-H insertion have limited information without a careful comparison of all possible pathways and just focused on certain steps. Building on our group’s recent mechanistic work on a number of heme carbene transfer reactions, we performed a quantum chemical study to systematically study all possible reaction pathways for myoglobin catalyzed N-H insertions, which starts from the reactants to final released products and thus constitute a complete reaction pathway study. We examined ylide (proton transfer), hydrogen atom transfer, and hydride transfer pathways. In the favored ylide pathways, we calculated the direct proton transfer from amine to carbene and indirect paths with both concerted and stepwise proton transfer and dissociation components. For the indirect pathways in which the proton resides on the carbonyl oxygen of the original carbene substituent, subsequent water-assisted proton transfer from this carbonyl oxygen to carbene’s carbon to form the final product was also investigated. The most favorable pathway from this systematic reaction mechanism study was further supported by new experimental work from our collaborators, the original developer of myoglobin-based biocatalysts. These novel mechanistic results provide important mechanistic information for future biocatalyst design with enhanced reactivities.

Site-selective α-C(sp3)-H arylation of dialkylamines via hydrogen atom transfer catalysis-enabled radical aryl migration.

Site-selective C(sp3)-H arylation is an appealing strategy to synthesize complex arene structures but remains a challenge facing synthetic chemists. Here we report the use of photoredox-mediated hydrogen atom transfer (HAT) catalysis to accomplish the site-selective α-C(sp3)-H arylation of dialkylamine-derived ureas through 1,4-radical aryl migration, by which a wide array of benzylamine motifs can be incorporated to the medicinally relevant systems in the late-stage installation steps. In contrast to previous efforts, this C-H arylation protocol exhibits specific site-selectivity, proforming predominantly on sterically more-hindered secondary and tertiary α-amino carbon centers, while the C-H functionalization of sterically less-hindered N-methyl group can be effectively circumvented in most cases. Moreover, a diverse range of multi-substituted piperidine derivatives can be obtained with excellent diastereoselectivity. Mechanistic and computational studies demonstrate that the rate-determining step for methylene C-H arylation is the initial H atom abstraction, whereas the radical ipso cyclization step bears the highest energy barrier for N-methyl functionalization. The relatively lower activation free energies for secondary and tertiary α-amino C-H arylation compared with the functionalization of methylic C-H bond lead to the exceptional site-selectivity.

Heterogeneous Electrosynthesis of Nitriles through Coupling of Primary Alcohols and Ammonia on Noble-Metal-Free Monometallic Catalyst

Despite increasing interest devoted to the electrocatalytic refinery of renewable feedstocks for the sustainable production of value-added chemicals, the direct electrosynthesis of nitriles from biomass-derived alcohols is rarely studied. Nitriles are highly versatile intermediates for producing a wide range of chemicals, including biological materials, pharmaceuticals and polymers. The conventional chemical methods for nitrile synthesis, such as the Sandmeyer and the Rosenmund-von Braun reactions, are not benign as they utilize toxic starting materials, require severe reaction conditions and generate large amounts of chemical waste. More environmentally friendly chemical routes using alcohols and ammonia as the substrates, via oxidation or oxidant-free dehydrogenation coupled with imination, have been recently reported. However, they face certain issues, including the need for oxidants or high reaction temperatures, as well as poor selectivity due to possible over-oxidation and other side reactions. On the electrocatalysis front, the synthesis of hydrogen cyanide, an analogue of nitrile, has been demonstrated using methanol and ammonia as the substrates, albeit at an elevated temperature with costly solid electrolytes. Here, we report a benign one-pot synthesis of nitriles from primary alcohols and ammonia, in the presence of a simple nickel electrocatalyst under ambient temperature using aqueous electrolytes without the need for oxidants.In the initial screening stage, nine species of metal-based catalysts which were reported to be active in the thermocatalytic pathway of the same reaction, including Mn, Fe, Co, Ni, Cu, Zn, Ru, Pd and Pt, as well as carbon paper were studied using benzyl alcohol (BnOH) as a model compound (Figure 1a). Among them, Ni foam, bearing good resistances towards dissolution under oxidative potentials and poisoning by ammonia, has the capacity to produce benzonitrile as the main product under lower overpotentials. Several control experiments were conducted, revealing that the reaction pathway proceeds via two sequential steps: (1) The alcohol first undergoes dehydrogenation to produce an aldehyde intermediate, which equilibrates in the presence of ammonia to afford the corresponding imine. (2) The imine is subsequently dehydrogenated to form the nitrile product (Figure 1b). Based on the linear sweep voltammetry (LSV) results and in-situ Raman analyses (Figure 1c, d), we propose that the in-situ formed NiII/NiIII redox species serve as the active sites for the nitrile production through a hydrogen atom transfer (HAT) mechanism. The influences of applied potentials, alcohol/ammonia concentrations and pH on the reaction were also systematically investigated. A high benzonitrile faradaic efficiency (FE) of 63.0% and a formation rate of 90.8 mmol m-2 h-1 were achieved at applied potentials of 1.375 V and 1.425 V vs. RHE, respectively, under the optimum conditions: 20 mM BnOH, 1 M ammonia and pH 13 (Figure 1e). Subsequently, kinetic studies and mathematical modelling were performed, suggesting that the dehydrogenation from alcohol to aldehyde displays the smallest rate constant. Isotope labelling experiments (Figure 1f) further confirmed that the rate-determining step (RDS) likely involves the cleavage of α-carbon C-H bond in the hydroxyl group of the alcohol. Encouragingly, various aromatic, aliphatic and heterocyclic primary alcohols were transformed to the corresponding nitriles, exhibiting the broad feasibility of our strategy. This study offers a promising electrocatalytic system for the low-cost, green synthesis of high-value nitriles in the chemical industry. Figure 1

Electro-Oxidation of Cumene Using Diamond Electrodes in Batch and Flow

Selective oxidation of aromatic alkyl side chains is an important molecular transformation process to obtain various materials ranging from rubber and resin to fine chemicals. Generally, molecular oxygen has been utilized in straightforward oxidation of aromatic alkyls. However, since molecular oxygen is highly stable, activation of the molecular oxygen itself is necessary, which requires a specific catalyst and/or harsh condition such as high temperature and high pressure. Recent environmental and sustainable concerns lead to a growing demand for the development of greener oxidation processes.Recently, electro-organic synthesis, referring to an organic synthesis method combined with electrochemistry, has drawn attention as a sustainable synthetic method. Since electro-organic synthesis utilizes electricity itself as a reagent, reactions proceed well even under ambient conditions and reagent wastes are reduced to a minimum. In electro-organic synthesis, electrode materials are one of the most significant parameters because reactions occur at the anode and/or cathode. Boron-doped diamond (BDD) is a relatively new electrode material and shows a wide potential window, which can be applied to the transformation of compounds with high redox potentials. Therefore, BDD electrodes would enable a straightforward oxidation reaction of aromatic alkyls, which is difficult to achieve with other conventional electrode materials.Herein, we report the straightforward electro-oxidation of cumene, one of the most important and extensively investigated aromatic alkyls, by BDD electrodes. The role of electrode materials was investigated with electrochemical measurements. Furthermore, the cell design (i.e. batch vs. flow) was examined, and we realized that the product selectivity of cumene oxidation can be switched by simply changing the cell design.First, we carried out the electrolysis of cumene under the constant current condition in an undivided batch cell. The main product was acetophenone under the following optimum conditions: (solvent) MeCN, (supporting electrolyte) Et4NClO4, (current density) 2.1 mA/cm2, (amount of charge) 5 F referring to mole of cumene. It should be noted that almost no acetophenone was obtained when the combination of anode and cathode was graphite/graphite or Ni/Ni. Cyclic voltammetry using BDD as a working electrode showed a clear oxidation peak of cumene at around 2.40 V (vs. Ag/Ag+). On the other hand, no clear oxidation peak was observed when using graphite or Ni as a working electrode. This is because potential windows of graphite and Ni are too narrow to oxidize cumene directly. Overall, the electrochemical measurements indicate the BDD’s wide potential window enables direct oxidation of cumene to produce a key reaction intermediate to afford acetophenone. A series of electrolysis experiments confirmed that the reaction intermediate is the cumyl cation and the oxygen source is the superoxide generated by reduction of dissolved oxygen on the cathode. A proposed mechanism is as follows. Anodic oxidation of cumene on the BDD electrode affords a cumyl cation. On the other hand, cathodic reduction of dissolved oxygen produces the superoxide and even the hydroperoxide anion. Addition of the hydroperoxide anion to the cumyl cation yields cumene hydroperoxide, which is further converted into acetophenone.Second, we carried out the electrolysis of cumene under the constant current condition in an undivided flow cell. The main product was a-cumyl alcohol under the following optimum conditions: (solvent) MeCN, (supporting electrolyte) Et4NClO4, (current density) 0.25 mA/cm2, (amount of charge) 1 F referring to mole of cumene, (flow rate) 0.375 mL/min. A series of flow electrolysis experiments indicated that cumene is converted into a-cumyl alcohol via cumene hydroperoxide, and then to acetophenone, which is supported by cyclic voltammetry measurements: the potential at which the current value increases was lower in the order of cumene hydroperoxide > a-cumyl alcohol > cumene > acetophenone. A proposed mechanism is as follows. A hydroperoxide anion generated at the cathode added to a cumyl cation generated at the anode to form cumene hydroperoxide. The O-O bond in cumene hydroperoxidewas cleaved anodically to form alkoxy radical, which underwent a hydrogen atom transfer (HAT) between cumene to yield a-cumyl alcohol and cumyl radical. Furthermore, a-cumyl alcoholwas oxidized into the alkoxy radical, followed by b-scission to yield acetophenone. Therefore, it is suggested that the selective conversion of cumene into a-cumyl alcohol in flow electrolysis was due to suppressing overoxidation of a-cumyl alcoholinto acetophenone. Figure 1

(Invited) Development of Leuco Ethyl Violet as Self-Activating Prodrug Photooxygenation Catalyst of Amyloid-β

Abnormal aggregation of amyloid-β (Aβ) and tau protein (tau), called amyloid, is characteristic of Alzheimer's disease (AD). Reducing amyloid levels in AD patients is expected to be an effective approach to AD treatment. To inhibit the hydrophobic interaction of amyloid, which is the cause of toxic aggregates, we planed to generate singlet oxygen by activating oxygen in vivo through photocatalysis, thereby introducing oxygen atoms to amyloid protein and inhibiting aggregation. In accordance with this concept, we are developing photooxygenation catalysts with a switch function that generates singlet oxygen only in the presence of amyloids. We have succeeded in reducing amyloid in AD model mouse brain non-invasively with this photo-oxygenation catalyst. However, moderate catalytic activity and the side effect of scalp damage have been problematic. This time, we identified leucoethyl violet (LEV) as a highly active, amyloid-selective, blood-brain barrier (BBB)-permeable photooxygenation catalyst. LEV is a self-activating procatalyst by external redox stimuli. Autoxidation of LEV by a hydrogen atom transfer process under light irradiation produced active catalyst species Ethyl Violet (EV) only in the presence of amyloids. LEV showed higher catalytic activity than the previously developed photooxygenation catalyst and realized oxygenation of human Aβ and tau. Taking advantage of LEV's high activity and amyloid selectivity, improved BBB permeability, and low cytotoxicity, photooxygenation of Aβ was achieved in an AD model without scalp injury. Figure 1

Lewis-Acid-Promoted Visible-Light-Mediated C(sp3)-H Bond Functionalization of Arylvinylpyridines via Diradical Hydrogen Atom Transfer.

A visible-light-induced intramolecular diradical-mediated hydrogen atom transfer (DHAT) of primary, secondary, and tertiary C(sp3)-H bonds and subsequent cyclization is described. This transformation is enabled by triplet energy transfer upon Lewis acid coordination to alkyl-substituted arylvinylpyridines and gives access to a variety of benzocyclobutenes (>40 examples, 32-96% yield). Notably, tri- and tetrasubstituted olefins with tertiary C(sp3)-H bonds effectively delivered sterically hindered products with adjacent all-carbon quaternary centers. Mechanistic evidence and density functional theory (DFT) calculations suggest that Lewis acid coordination was crucial for the success by modulating the reactivity of the diradical intermediates to unlock a challenging carbon-to-carbon DHAT and subsequent cyclization with a rather low barrier, which allows the functionalization of benzylic C(sp3)-H bonds to construct otherwise inaccessible benzocyclobutenes.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Nickel-Catalyzed Radical Hydroalkylative Dearomatization of Indoles with Alkyl Bromides

Dearomatization of indole derivatives offers a straightforward approach to accessing indoline framework. However, highly efficient dearomatization of indoles bearing electron-deficient groups remains underdeveloped. Herein, a nickel-catalyzed intermolecular hydroalkylative dearomatization reaction of indoles with simple alkyl bromides via single-electron-transfer process is reported. A wide variety of indole derivatives bearing versatile functional groups were compatible with this protocol, by reacting with primary, secondary, and tertiary bromides to afford a series of indolines in good yields (up to 82%) with excellent diastereoselectivity (up to >20:1). Notably, a nickel-mediated hydrogen atom transfer process was observed when terminal bromides were employed as the radical precursors, which resulted in the branched products.

Mechanism of the Oxidative Ring-Closure Reaction during Gliotoxin Biosynthesis by Cytochrome P450 GliF.

During gliotoxin biosynthesis in fungi, the cytochrome P450 GliF enzyme catalyzes an unusual C-N ring-closure step while also an aromatic ring is hydroxylated in the same reaction cycle, which may have relevance to drug synthesis reactions in biotechnology. However, as the details of the reaction mechanism are still controversial, no applications have been developed yet. To resolve the mechanism of gliotoxin biosynthesis and gain insight into the steps leading to ring-closure, we ran a combination of molecular dynamics and density functional theory calculations on the structure and reactivity of P450 GliF and tested a range of possible reaction mechanisms, pathways and models. The calculations show that, rather than hydrogen atom transfer from the substrate to Compound I, an initial proton transfer transition state is followed by a fast electron transfer en route to the radical intermediate, and hence a non-synchronous hydrogen atom abstraction takes place. The radical intermediate then reacts by OH rebound to the aromatic ring to form a biradical in the substrate that, through ring-closure between the radical centers, gives gliotoxin products. Interestingly, the structure and energetics of the reaction mechanisms appear little affected by the addition of polar groups to the model and hence we predict that the reaction can be catalyzed by other P450 isozymes that also bind the same substrate. Alternative pathways, such as a pathway starting with an electrophilic attack on the arene to form an epoxide, are high in energy and are ruled out.

Photocatalytic Asymmetric Acyl Radical Truce–Smiles Rearrangement for the Synthesis of Enantioenriched α‐Aryl Amides

AbstractThe radical Truce–Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non‐expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce–Smiles rearrangement of α‐substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom–transfer photocatalyst, along with aldehydes or C−H containing precursors. The rearranged products exhibited excellent diastereoselectivities (7 : 1 to >98 : 2 d.r.) and chiral auxiliary was easily removed. Mechanistic studies allowed understanding the transformation in which density functional theory (DFT) calculations provided insights into the stereochemistry‐determining step.

Photocatalytic Asymmetric Acyl Radical Truce-Smiles Rearrangement for the Synthesis of Enantioenriched α-Aryl Amides.

The radical Truce-Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non-expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce-Smiles rearrangement of α-substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom-transfer photocatalyst, along with aldehydes or C-H containing precursors. The rearranged products exhibited excellent diastereoselectivities (7 : 1 to >98 : 2 d.r.) and chiral auxiliary was easily removed. Mechanistic studies allowed understanding the transformation in which density functional theory (DFT) calculations provided insights into the stereochemistry-determining step.

Cobalt‐Catalyzed Intramolecular Markovnikov Hydrocarbonylation of Unactivated Alkenes via Hydrogen Atom Transfer

A cobalt‐catalyzed intramolecular Markovnikov hydroalkoxycarbonylation and hydroaminocarbonylation of unactivated alkenes has been developed, enabling highly chemo‐ and regioselective synthesis of α‐alkylated γ‐lactones and α‐alkylated γ‐lactams in good yields. The mild reaction conditions allow use of mono‐, di‐ and trisubstituted alkenes bearing a variety of functional groups. Preliminary mechanistic studies suggest the reaction proceeds through a CO‐mediated hydrogen atom transfer (HAT) and radical‐polar crossover (RPC) process, in which a cationic acylcobalt(IV) complex is proposed as the key intermediate.

Cobalt-Catalyzed Intramolecular Markovnikov Hydrocarbonylation of Unactivated Alkenes via Hydrogen Atom Transfer.

A cobalt-catalyzed intramolecular Markovnikov hydroalkoxycarbonylation and hydroaminocarbonylation of unactivated alkenes has been developed, enabling highly chemo- and regioselective synthesis of α-alkylated γ-lactones and α-alkylated γ-lactams in good yields. The mild reaction conditions allow use of mono-, di- and trisubstituted alkenes bearing a variety of functional groups. Preliminary mechanistic studies suggest the reaction proceeds through a CO-mediated hydrogen atom transfer (HAT) and radical-polar crossover (RPC) process, in which a cationic acylcobalt(IV) complex is proposed as the key intermediate.

CdS Quantum Dot Gels as a Direct Hydrogen Atom Transfer Photocatalyst for C-H Activation.

Here, we report CdS quantum dot (QD) gels, a three-dimensional network of interconnected CdS QDs, as a new type of direct hydrogen atom transfer (d-HAT) photocatalyst for C-H activation. We discovered that the photoexcited CdS QD gel could generate various neutral radicals, including α-amido, heterocyclic, acyl, and benzylic radicals, from their corresponding stable molecular substrates, including amides, thio/ethers, aldehydes, and benzylic compounds. Its C-H activation ability imparts a broad substrate and reaction scope. The mechanistic study reveals that this reactivity is intrinsic to CdS materials, and the neutral radical generation did not proceed via the conventional sequential electron transfer and proton transfer pathway. Instead, the C-H bonds are activated by the photoexcited CdS QD gel via a d-HAT mechanism. This d-HAT mechanism is supported by the linear correlation between the logarithm of the C-H bond activation rate constant and the C-H bond dissociation energy (BDE) with a Brønsted slope α=0.5. Our findings expand the currently limited direct hydrogen atom transfer photocatalysis toolbox and provide new possibilities for photocatalytic C-H activation.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.

Visible‐Light‐Mediated Activation of Remote C(sp3)−H Bonds by Carbon‐Centered Biradical via Intramolecular 1,5‐ or 1,6‐Hydrogen Atom Transfer

AbstractIn this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish‐Yang reaction. This process is facilitated by excited triplet‐state carbon‐centered biradicals, enabling the 1,5‐HAT reaction by suppressing the critical 1,4‐biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6‐HAT reactions initiated by excited triplet‐state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large‐scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern–Volmer experiments, and density functional theory (DFT) calculations.