Single Electron Transfer Oxidation Research Articles

1,3-Difunctionalization of [1.1.1]propellane through iron-hydride catalyzed hydropyridylation

Current methodologies for the functionalization of [1.1.1]propellane primarily focus on achieving 1, 3-difunctionalized bicyclo[1.1.1]pentane or ring-opened cyclobutane moiety. Herein, we report an innovative approach for the 1, 3-difunctionalization of [1.1.1]propellane, enabling access to a diverse range of highly functionalized cyclobutanes via nucleophilic attack followed by ring opening and iron-hydride hydrogen atom transfer. To enable this method, we developed an efficient iron-catalyzed hydropyridylation of various alkenes for C − H alkylation of pyridines at the C4 position, eliminating the need for stoichiometric quantities of oxidants or reductants. Mechanistic investigations reveal that the resulting N-centered radical serves as an effective oxidizing agent, facilitating single-electron transfer oxidation of the reduced iron catalyst. This process efficiently sustains the catalytic cycle, offering significant advantages for substrates with oxidatively sensitive functionalities that are generally incompatible with alternative approaches. The strategy presented herein is not only mechanistically compelling but also demonstrates broad versatility, highlighting its potential for late-stage functionalization.

Decoupling Plasmonic Hot Carrier from Thermal Catalysis via Electrode Engineering.

Increased attention has been directed toward generating nonequilibrium hot carriers resulting from the decay of collective electronic oscillations on metal known as surface plasmons. Despite numerous experimental endeavors, demonstrating hot carrier-mediated photocatalysis without a heating contribution has proven challenging, particularly for single electron transfer reactions where the thermal contribution is generally detrimental. An innovative engineering solution is proposed to enable single electron transfer reactions with plasmonics. It consists of a photoelectrode designed as an energy filter and photocatalysis performed with light function modulation instead of continuously. The photoelectrode, consisting of FTO/TiO2 amorphous (10 nm)/Au nanoparticles, with TiO2 acting as a step-shape energy filter to enhance hot electron extraction and charge-separated state lifetime. The extracted hot electrons were directed toward the counter electrode, while the hot holes performed a single electron transfer oxidation reaction. Light modulation prevented local heat accumulation, effectively decoupling hot carrier catalysis from the thermal contribution.

Visible‐Light‐Driven Formyl Group Migration Triggered Remote Desaturation

Dehydrogenation of unactivated alkanes to form versatile alkenes is an important but challenging task in synthetic chemistry. Enabled by a radical‐mediated formyl group migration, a novel visible light‐induced remote desaturation of aldehydes is developed, delivering a panel of trifluoromethylated δ,ε‐ or γ,δ‐unsaturated aldehydes in moderate to excellent yields with good functional group tolerance at room temperature. Mechanistic studies indicate a reaction pathway comprising the cascade trifluoromethylation of C‐C double bonds, intramolecular addition to aldehydes, β‐fragmentation of alkoxy radicals, single electron transfer oxidation, and deprotonation. It provides a good complementary approach to the existing desaturation protocols.

Mechanistic insight into the degradation of sulfadiazine by electro-Fenton system: Role of different reactive species

Sulfadiazine (SDZ), a widely used effective antibiotic, is resistant to conventional biological treatment, which is concerning since untreated SDZ discharge can pose a significant environmental risk. Electro-Fenton (EF) technology is a promising advanced oxidation technology for efficiently removing SDZ. However, due to the limitations of traditional experimental methods, there is a lack of in-depth study on the mechanism of ·OH-dominated SDZ degradation in EF process. In this study, an EF system was established for SDZ degradation and the transformation products (TPs) were detected by mass spectrometry. Dynamic thermodynamic, kinetic and wave function analysis of reactants, transition states and intermediates were proposed by density functional theory calculations, which was applied to elucidate the underlying mechanism of SDZ degradation. Experimental results showed that amino, benzene, and pyrimidine sites in SDZ were oxidized by ·OH, producing TPs through hydrogen abstraction and addition reactions. ·OH was kinetically more likely to attack SDZ- than SDZ. Fe(IV) dominated the single-electron transfer oxidation reaction of SDZ, and the formed organic radicals can spontaneously generate the de-SO2 product via Smiles rearrangement. Toxicity experiments showed the toxicity of SDZ and TPs can be greatly reduced. The results of this study promote the understanding of SDZ degradation mechanism in-depth. Environmental ImplicationSulfadiazine (SDZ) is one of the antibiotics widely used around the world. However, it has posed a significant environmental risk due to its overuse and cannot be efficiently removed by traditional treatment methods. The lack of in-depth study on SDZ degradation mechanism under reactive species limits the improvement of SDZ degradation efficiency. Therefore, this work focused on SDZ degradation mechanism in-depth under electro-Fenton system through reactive species investigation, mass spectrometry analysis, and theoretical calculation. The results in this study can provide a theoretical basis for improving the SDZ degradation efficiency which will contribute to solving SDZ pollution problems.

Oxidase-like manganese oxide nanoparticles: a mechanism of organic acids/aldehydes as electron acceptors and potential application in cancer therapy.

Identifying the underlying catalytic mechanisms of synthetic nanocatalysts or nanozymes is important in directing their design and applications. Herein, we revisited the oxidation process of 4,4'-diamino-3,3',5,5'-tetramethylbiphenyl (TMB) by Mn3O4 nanoparticles and revealed that it adopted an organic acid/aldehyde-triggered catalytic mechanism at a weakly acidic or neutral pH, which is O2-independent and inhibited by the pre-addition of H2O2. Importantly, similar organic acid/aldehyde-mediated oxidation was applied to other substrates of peroxidase in the presence of nanoparticulate or commercially available MnO2 and Mn2O3 but not MnO. The selective oxidation of TMB by Mn3O4 over MnO was further supported by density functional theory calculations. Moreover, Mn3O4 nanoparticles enabled the oxidation of indole 3-acetic acid, a substrate that can generate cytotoxic singlet oxygen upon single-electron transfer oxidation, displaying potential in nanocatalytic tumor therapy. Overall, we revealed a general catalytic mechanism of manganese oxides towards the oxidation of peroxidase substrates, which could boost the design and various applications of these manganese-based nanoparticles.

Hypervalent iodine mediated Pd(II)‐catalyzed ortho‐C(sp2−H) functionalization of azoles deciphering Hantzsch ester and malononitrile as the functional group surrogates

AbstractC−H bond activation has surfaced as a transformative toolbox for the efficient assembly of biologically important molecules. However, despite of major advances in palladium, rhodium and silver catalysis, yet palladium(II)‐ catalyzed, iodobenzene diacetate (PIDA) mediated C−H bond activation in azole skeleton has deluged with interesting wining outcome. Concentrating on that we herein report on the involvement of 4‐functionalized 1,4‐dihydropyridines (R‐DHPs) as the representative surrogates of benzoyl, pivalyl and ethoxycarbonyl groups and in presence of PIDA it releases appropriate functional radical (following single electron transfer oxidation of R‐DHPs under thermal condition)to become the part of ortho‐ functionalized azoles via Pd(II) catalysis. In case of cyanation reaction, malononitrile has served the key source of nitrile functionality by undergoing oxidative C−CN bond cleavage in presence of PIDA and with the help of Pd(II) catalyst it offers ortho‐cyanated azoles. Additionally, the selective formation of C‐3 benzoyl and ester functionalized indazole derivatives in absence of Pd(II)‐catalyst and the unprecedented formation of homo‐coupling products between two identical 2H‐indazoles are also notable outcome of present strategic access. Overall this protocol operates under mild condition, tolerates a wide range of structural moieties and gives versatile azole derivatives in high efficiency. The antioxidant properties of the synthesized 2‐thiophenyl benzoyl selenazole and isoselenazole are further evaluated using a chemically defined method. The Copper‐ascorbate (Cu−As) was utilized as an oxidative stress generator. Out of screened azoles, the 2‐benzoyl isoselenazole compound (3 i) displays magnificent antioxidant property as compared to the 2‐thiophenyl benzoyl selenazole (3 g).

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis.

Photocatalysis opens up a new window for carbonyl chemistry. Despite a multitude of photochemical reactions of carbonyl compounds, visible light-induced catalytic asymmetric transformations remain elusive and pose a formidable challenge. Accordingly, the development of simple, efficient, and economic catalytic systems is the ideal pursuit for chemists. Herein, we report an enantioselective radical photoaddition to ketones through a Lewis acid-enabled photoredox catalysis wherein the in situ formed chiral N,N'-dioxide/Sc(III)-ketone complex serves as a temporary photocatalyst to trigger single-electron transfer oxidation of silanes for the generation of nucleophilic radical species, including primary, secondary, and tertiary alkyl radicals, giving various enantioenriched aza-heterocycle-based tertiary alcohols in good to excellent yields and enantioselectivities. The results of electron paramagnetic resonance (EPR) and high-resolution mass spectrum (HRMS) measurements provided favorable evidence for the stereocontrolled radical addition process involved in this reaction.

Switchable Radical Carbonylation by Philicity Regulation.

Carbonylation reactions involving CO as readily available C1 synthons have become one of the most important tools for the construction of carbonyl compounds from feedstock chemicals. Despite numerous catalytic methods for carbonylation reactions proceeding via ionic or radical pathways, an inherent limitation to these methods is the need to control switchable single and double carbonylative formation of value-added products from the same and simple starting materials. Here, we describe a new strategy that exploits photoredox catalysis to regulate the philicity of amine coupling partners to drive switchable radical carbonylation reactions. In double carbonylation, amines were first transformed into nitrogen radical cations by single-electron transfer-oxidation and coupled with CO to form carbamoyl radicals, which further underwent radical cross-coupling with the incipient cyanoalkyl acyl radicals to afford the double carbonylation products. Upon the addition of stoichiometric 4-dimethylaminopyridine (DMAP), DMAP competitively traps the initially formed cyanoalkyl acyl radical to form the relatively stabilized cyanoalkyl acyl-DMAP salts that engaged in the subsequent substitution with the nucleophilic amines to produce the single carbonylation products. The reaction proceeded smoothly with excellent selectivity in the presence of various amine nucleophiles at room temperature, generating valuable amides and α-ketoamides in a versatile and controlled fashion. Combined experimental and computational studies provided mechanistic insights into the possible pathways.

1,4-Aryl migration in ketene-derived enolates by a polar-radical-crossover cascade

The arylation of carboxylic acid derivatives via Smiles rearrangement has gained great interest in recent years. Both radical and ionic approaches, as well as radical-polar crossover concepts, have been developed. In contrast, a reversed polar-radical crossover approach remains underexplored. Here we report a simple, efficient and scalable method for the preparation of sterically hindered and valuable α-quaternary amides via a polar-radical crossover-enolate oxidation-aryl migration pathway. A variety of easily accessible N-alkyl and N-arylsulfonamides are reacted with disubstituted ketenes to give the corresponding amide enolates, which undergo upon single electron transfer oxidation, a 1,4-aryl migration, desulfonylation, hydrogen atom transfer cascade to provide α-quaternary amides in good to excellent yields. Various mono- and di-substituted heteroatom-containing and polycyclic arenes engage in the aryl migration reaction. Functional group tolerance is excellent and substrates as well as reagents are readily available rendering the method broadly applicable.

Chemistry with Electrochemically Generated N-Centered Radicals.

N-centered radicals are versatile reaction intermediates that can react with various π systems to construct C-N bonds. Current methods for generating N-centered radicals usually involve the cleavage of an N-heteroatom bond; however, similar strategies that are applicable to N-H bonds prove to be more challenging to develop and therefore are attracting increasing attention. In this Account, we summarize our recent efforts in the development of electrochemical methods for the generation and synthetic utilization of N-centered radicals. In our studies, N-aryl amidyl radical, amidinyl radical and iminyl radical cation intermediates are generated from N-H precursors through direct electrolysis or indirect electrolysis assisted by a redox catalyst. In addition, an electrocatalytic method that converts oximes to iminoxyl radicals has also been developed. The electrophilic amidyl radical intermediates can participate in 5-exo or 6-exo cyclization with alkenes and alkynes to afford C-centered radicals, which can then undergo various transformations such as H atom abstraction, single-electron transfer oxidation to a carbocation, cyclization, or aromatic substitution, leading to a diverse range of N-heterocyclic products. Furthermore, amidinyl radicals, iminyl radical cations, and iminoxyl radicals can undergo intramolecular aromatic substitution to afford various N-heteroaromatic compounds. Importantly, the electrochemical reaction can be channeled toward a specific product despite the presence of other competing pathways. For a successful electrosynthesis, it is important to take into consideration of both the electron transfer steps associated with the electrode and the nonelectrode related processes. A unique feature of electrochemistry is the simultaneous occurrence of anodic oxidation and cathodic reduction, which, as this Account demonstrates, allows the dehydrogenative transformations to proceed through H2 evolution without the need for chemical oxidants. In addition, cathodic solvent reduction can continuously generate a low concentration of base, which facilitates anodic substrate oxidation. Such a mechanistic paradigm obviates the need for stoichiometric strong bases and avoids base-promoted decomposition of sensitive substrates or products. Furthermore, electrode materials can also be adjusted to control the reaction outcome, as demonstrated by the synthesis of N-heteroaromatics and the corresponding N-oxides from biaryl ketoximes.

Chemistry With N-Centered Radicals Generated by Single-Electron Transfer-Oxidation Using Photoredox Catalysis

This review covers the recent literature on oxidative generation of N-centered radicals using photoredox catalysis. The concept of proton-coupled electron transfer is briefly discussed. Applications of such reactive N-centered radicals in cascade processes comprising arene amidation, alkene amidation, C—C bond cleavage reactions, and remote C—H functionalization are addressed. In addition, novel reagents allowing for clean oxidative N-radical generation are discussed.

The synthesis of some novel stilbene dimers incorporating diamide tethers: studies in single electron transfer oxidation (FeCl3).

The FeCl3 oxidative cascade reaction of the acetamido stilbene 1 which we reported some years ago produced the first atropodiastereomeric indolostilbene hybrid 3. By contrast, recent investigation of the oxidation of the stilbene succinamide dimer 72 (FeCl3/CH2Cl2) appears, on the basis of spectroscopic evidence, to have produced the bridged macrocyclic indoline 73.

High efficiency solar chemical conversion using electrochemically disordered titania nanotube arrays transplanted onto transparent conductive oxide electrodes

Free-standing, one-dimensional TiO2 nanotube arrays (TNAs) with a disordered surface structure are synthesized on transparent conducting substrates, and their opto-physicochemical properties and photoelectrocatalytic (PEC) performances are examined in detail. A two-step anodization process is used to transplant TNAs grown on titanium foils onto fluorine-doped SnO2 substrates (denoted as W-TNAs), after which they are electrochemically reduced for 20 and 90 s (denoted as B-TNAs-20 and 90, respectively). The as-transplanted W-TNAs exhibit low PEC activities in terms of their photocurrent, oxygen evolution reaction (OER), and oxidations of inorganic and organic substrates (iodide and urea, respectively) under simulated sunlight (AM 1.5; 100 mW cm−2), primarily because of the sluggish charge transfer through the poor electrically conductive TNA framework. The quick electrochemical reduction of the W-TNAs leads to an 8-fold larger photocurrent, while significantly accelerating the OER (by three times) and iodide and urea oxidation reactions (by 2 and ∼20 times, respectively). These enhanced PEC activities of the B-TNAs are attributed to the creation of Ti3+ and associated oxygen vacancies which strengthen their n-type characteristics and thereby increase their electrical conductivity. The time-resolved photoluminescence spectra further reveal that the lifetime (τ) of the photogenerated charge carriers in the B-TNAs (τ = 0.33 ns) is an order of magnitude shorter than that of the W-TNAs (τ = 3.63 ns). The disordered surface exhibits a lower Faradaic efficiency for multi-electron transfer oxidation reactions and a higher Faradaic efficiency for single-electron transfer oxidation reactions compared to the W-TNAs. The detailed surface characterization and PEC mechanism are discussed.

Catalytic Asymmetric Synthesis of Fluoroalkyl-Containing Compounds by Three-Component Photoredox Chemistry.

Multicomponent reactions allow the construction of molecular complexity in an economical fashion, fluorinated compounds play an important role in pharmaceuticals and agrochemicals, whereas visible light is an abundant and sustainable source of energy for activating chemical transformations. Here we report a visible-light-induced asymmetric three-component fluoroalkylation reaction scheme catalyzed by a chiral-at-rhodium Lewis acid. The photoredox process is mediated by the inexpensive, commercially available organic photoredox mediator 4,4'-difluorobenzil, which upon activation by visible light induces the generation of perfluoroalkyl radicals from their sulfinates via single electron transfer oxidation. The fluorinated radicals are trapped by electron-rich C-C double bonds to deliver α-oxy carbon-centered radicals, followed by a subsequent stereocontrolled reaction with acceptor-substituted alkenes. This three-component fluoroalkylation scheme provides a range of complex fluoroalkyl-containing chiral compounds under dual C-C bond formation with high enantioselectivities (up to 98 % ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives are observed. Broad substrate scope (25 examples), excellent functional group tolerance, scalability of the reaction, along with the option to recover the chiral catalyst and photoredox mediator reveal the practicability of this methodology in organic synthesis for the rapid synthesis of fluorinated chiral molecules.

Transition metal-induced degradation of a pharmaceutical compound in reversed-phase liquid chromatographic analysis

Drug degradation that occurs in HPLC analysis, during either sample preparation or chromatographic separation, can greatly impact method robustness and result accuracy. In this work, we report a case study of drug dimerization in HPLC analysis where proximate causes were attributed to either the LC columns or the HPLC instrument. Solution stress studies indicated that the same pseudo-dimeric degradants could also be formed rapidly when the compound was exposed to certain oxidative transition metal ions, such as Cu(II) and Fe(III). Two pseudo-dimeric degradants were isolated from transition metal stressed samples and their structures were elucidated. A degradation pathway was proposed, whereby the degradation was initiated through transition metal-induced single electron transfer oxidation. Further studies confirmed that the dimerization was induced by trace transition metals in the HPLC flow path, which could arise from either the stainless steel frits in the LC column or stainless steel tubing in the HPLC instrument. Various procedures to prevent transition metal-induced drug degradation were explored, and a general strategy to mitigate such risks is briefly discussed.

Unexpected formation of a phenonium ion-containing salt by single electron-transfer oxidation of a cage compound possessing triphenylamine moieties

The phenonium ion-containing salt 6-Cl+SbCl6− was unexpectedly generated in the tris(4-bromophenyl)aminium hexachloroantimonate-promoted, single electron-transfer oxidation reaction of 9,10-bis(4-diphenylaminophenyl)tetracyclo[6.2.0.04,10.05,9]decane (5). X-ray crystallographic analysis and quantum chemical calculations reveal that the cation in 6-Cl+SbCl6− contains a unique bridging phenonium ion structure that is stabilized by the presence of a cross-conjugated N,N-diphenyldivinyliminium ion (3-diphenylamino-1,3-cyclohexadienyl cation). It is noteworthy that 6-Cl+SbCl6− is a trapped product of a phenonium like radical cation 6+, the radical cation mutant of 2+.

Enzyme-triggered Radical Reactions: Another Approach For Tin-free Radical Chemistry

The system laccase/mediator/dioxygen is able to trigger radical reactions with radical precursors which are not natural substrates of this enzyme. The radical generation has been accomplished by single electron transfer oxidation of a 1,3-dicarbonyl precursor. The process is exemplified with a radical cascade.

ChemInform Abstract: Direct Oxidative Conversion of 3‐Aryl Propionaldehydes to 3‐Aryl Acroleins Promoted by SOMO Catalysis.

AbstractThe transformation is efficiently achieved by an amine‐catalyzed CAN‐mediated single electron transfer oxidation process.

ChemInform Abstract: Electron Transfer Reactions of Piperidine Aminoxyl Radicals

AbstractReview: 160 refs.

Electron transfer reactions of piperidine aminoxyl radicals

This review article summarizes the electron transfer reactions of piperidine aminoxyl radicals. Electrochemical studies revealed the single electron transfer nature of piperidine aminoxyl radicals. In solution, piperidine aminoxyl radicals serve as single electron transfer oxidation reagent to react with various biologically interesting molecules such as glutathione, cysteine, ascorbic acid, and amines. The reaction product distribution, reaction kinetics, intermediates, and the reaction features in biological mimic environments including micelles and cyclodextrins were investigated. Oxoammonium salts, the one-electron transfer oxidation products of piperidine aminoxyl radicals, are agents of organic synthesis to selectively generate ketones or di-ketones from alcohols or ketones bearing α-methylene group under mild conditions. The new reactions of oxoammonium salts with aromatic amines, phenols, heterocycles including phenothiazines, papaverine, and bilirubin are also illustrated.