Single Electron Transfer Process Research Articles

A Direct Visible‐Light Mediated Coupling Of Azaarenes with Diversely Functionalized Alkyl Carbons via Organophotocatalytic Sp3C−H Bond Activation

AbstractSubstituted azaarenes are one of the most ubiquitous moieties in natural products and drug molecules. An efficient organophotocatalytic method for direct coupling of diverse cyclic and acyclic alkyl carbons of alcohols, ethers, alkyl halides and alkanes with different azaaryl systems has been developed. It uses low loading of easily synthesizable efficient acridinium based photocatalyst and blue LED to generate highly reactive radicals on saturated hydrocarbons through sequential single electron transfer (SET) and hydrogen atom transfer (HAT) process. These in situ generated nucleophilic carbon radicals then undergo instantaneous regio‐selective coupling with azaarenes through Minisci type coupling to generate an array of important pharmacophores through sp2C−sp3C bond formation. With inexpensive organophotocatalysts, higher yield and wide substrate scope, this method provides a greener, efficient and versatile alternative to the previously reported syntheses.

Photocatalyzed Arylthiolation/Cyclization of 3‐(2‐(Ethynyl)phenyl)Quinazolinones with Disulfides towards Arylthiolated Quinolino[2,1‐b]Quinazolinones

AbstractAn approach to the synthesis of arylthiolated quinolino[2,1‐b]quinazolinones has been developed using unactivated alkynes containing quinazolinones and diaryldisulfides under visible light irradiation. The procedure entails a sequential radical arylthiolation and cyclization reaction. A possible radical mechanism has been investigated and proven as a single electron transfer (SET) process.

Advances in Light Promoted Transformation of N-Heterocyclic Carbene-Ligated Boryl Radical

Organoboron compounds are integral to modern life, with extensive applications in synthesis, materials science, medicine, and various other domains closely linked to human endeavors. NHC-BH3, noted for its stability, ease of synthesis, and high reactivity as a boryl radical precursor, has emerged as a key focus in boryl radical chemistry. Recently, the visible-light-induced single electron transfer (SET) and hydrogen atom transfer (HAT) processes have garnered considerable interest, presenting innovative strategies for generating boryl radicals from NHC-BH3. In the context of this review, our focus is on the synthesis of C-B and X-B bonds under visible light irradiation, facilitated by NHC-BH3. Furthermore, we explored the role of NHC-BH3 as a hydrogen donor or halogen atom transfer reagent in the construction of C-C bond.

Photo‐and Electrochemical Modification of Amino Acids, Peptides and Proteins through Cysteine: Recent Advances and Future Perspectives

AbstractChemical modification of peptides and proteins has emerged as an efficient strategy to study and manipulate the physical and chemical properties and biological functionalities of proteins. Among the 20 proteinogenic amino acids, cysteine is one of the most frequently targeted residues for chemical modification of peptides and proteins due to its unique thiol group and its relatively low natural abundance. Cysteine is able to partake in radical and atom‐, electron‐ and hydride‐transfer reactions taking the benefit of redox activity of thiol side chain. Recently, photo‐ and electrochemistry have emerged as influential methodologies for enabling novel transformations in organic synthesis. These two fields both involve the generation of radical intermediates through single electron transfer processes, which align well with the redox activity of cysteine residue. Furthermore, the mild and controllable features are suitable for solving the chemo‐ and regioselective problems of the existing bioconjugation strategies. Given the intrinsic benefits of photo‐ and electrochemical redox catalysis, the application of developing novel cysteine‐based bioconjugation methods is increasingly compelling. This review provides a comprehensive overview of recent advancements in photo‐ and electrochemical approaches for modifying cysteine amino acid residues, cysteine‐containing peptides, and proteins. The advantages of photo‐ and electrochemical redox catalysis and its applicability in developing novel biocompatible methods are discussed. Additionally, the current limitations of these methods and the challenges that need to be addressed in the future are also explored.

Light-Driven N-Heterocyclic Carbene-Catalyzed Multi-Component Reaction for the Synthesis of β-Amino Ketones.

A N-heterocyclic carbene-catalyzed (NHC) three-component reaction involving N-aminopyridinium salts, alkenes, and aldehydes for the synthesis of β-amino ketones is described. In this reaction, N-aminopyridinium salts and the Breslow intermediate, which is generated from NHC and aldehydes, are utilized to undergo a single-electron transfer process, forming a ketyl radical intermediate and amidyl radicals. Subsequent to the formation of the amidyl radical, it undergoes selective capture by alkenes, followed by radical cross-coupling to yield the desired β-amino ketones.

Influence of 1,2,4-Tri-tert-butylcyclopentadienyl Ligand on the Reactivity of the Thorium Bipyridyl Metallocene [η5-1,2,4-(Me3C)3C5H2]2Th(bipy)

The thorium bipyridyl metallocene (Cp3tBu)2Th(bipy) (1; Cp3tBu = η5-1,2,4-(Me3C)3C5H2) shows a rich reactivity toward a series of small molecules. For example, complex 1 may act as a synthon for the (Cp3tBu)2Th(II) fragment as illustrated by its reactivity toward to CuI, hydrazine derivative (PhNH)2, Ph2E2 (E = S, Se), elemental sulfur (S8) and selenium (Se), organic azides, CS2, and isothiocyanates. Moreover, in the presence of polar multiple bonds, such as those in ketones Ph2CO and (CH2)5CO, aldehydes p-MePhCHO and p-ClPhCHO, seleno-ketone (p-MeOPh)2CSe, nitriles PhCN, Ph2CHCN, C6H11CN, and p-(NC)2Ph, and benzoyl cyanide PhCOCN, C-C coupling occurs to furnish (Cp3tBu)2Th[(bipy)(Ph2CO)] (10), (Cp3tBu)2Th[(bipy)((CH2)5CO)] (11), (Cp3tBu)2Th[(bipy)(p-MePhCHO)] (12), (Cp3tBu)2Th[(bipy)(p-ClPhCHO)] (13), (Cp3tBu)2Th[(bipy){(p-MeOPh)2CSe}] (14), (Cp3tBu)2Th[(bipy)(PhCN)] (16), (Cp3tBu)2Th[(bipy)(Ph2CHCN)] (17), (Cp3tBu)2Th[(bipy)(C6H11CN)] (18), [(Cp3tBu)2Th]2{μ-(bipy)[p-Ph(CN)2](bipy)} (20), and (Cp3tBu)2Th{(bipy)[PhC(CN)O]} (21), respectively. Nevertheless, ketazine (PhCH═N)2 or benzyl nitrile PhCH2CN forms the dimeric complexes [(Cp3tBu)Th]2[μ-NC(Ph)(bipy)]2 (15) and (Cp3tBu)2Th[(bipy){C(═CHPh)NH}] (19), respectively. In contrast, C-N bond cleavage and C-C coupling processes occur upon addition of isonitriles Me3CNC and C6H11NC to 1 to yield the thorium isocyanido amido complexes (Cp3tBu)2Th[4-(Me3C)bipy](NC) (22) and (Cp3tBu)2Th[4-(C6H11)bipy](NC) (23), respectively. Furthermore, a single-electron transfer (SET) process ensues when 1 equiv of CuI is added to 1 to yield the Th(VI) bipyridyl iodide complex (Cp3tBu)2Th(I)(bipy) (3).

At the Speed of Light: Recent Advances on Photocatalyzed Generation and Applications of Iminyl Radicals Promoted by Visible-light

: Nitrogen-positioned radicals are chemical entities that have a lengthier history than carbon ones and their high reactivity makes them invaluable. But, despite its power, much of its chemistry is still uncharted. Currently, developed methodologies to access nitrogen-positioned radicals, such as transition metal catalysis or visible-light photoredox methods through a single-electron transfer process, avoiding the use of harmful or toxic reagents, excess raw materials, solvents as well as pre-functionalization steps or extensive synthetic routes are in continuous progress. This revision aims to depict the recent advances in the field of iminyl-radicals’ syntheses, a special class of radicals placed on nitrogen, catalyzed by transition metals or photoredox techniques for the construction of C-N bonds and their synthetic applications. This work serves as a comprehensive guide for the scope of synthetic applications that this kind of radicals could have.

Research Progress on the Formation of C-C Bonds through Photoinduced Cross-coupling Reactions Involving Katritzky Salts

Abstract: In recent years, photochemical organic conversion promoted by visible light has attracted the interest of many organic chemists. Compared with the traditional methods, visible light as the photocatalytic oxidation of renewable energy has been proved to be a mild and powerful tool that can promote the activation of organic molecules through the single electron transfer (SET) process. Katritzky salt has been widely used in organic synthesis and drug preparation due to its convenient synthesis, easy availability of raw materials and high stability. These large Katritzky salts derived from amines can easily generate carbon radicals and conduct various organic conversion reactions. At present, this research has become an important research field of organic synthesis. This paper reviews the research results of coupling reactions of Carbon- Carbon bond formation involving visible light promoted Katritzky salts since 2020, and discusses representative examples and reaction mechanisms.

Photoinduced Hydrosilylation of Fluorinated Alkenes.

A visible-light-induced synthesis protocol for silylmonofluoroalkanes is described. The silylation of alkenyl fluorides using (trimethylsilyl)silanes as organosilicon reagents proceeds well under mild conditions via a sequential photoinduced single-electron transfer and protonation process. The protocol shows a broad substrate scope, transition-metal-free conditions, and high functional group tolerance. A wide variety of silylmonofluoroalkanes were obtained in generally good yields (up to 82%).

Iron-Catalyzed Deboronation/Cyanoalkylation of Vinyl Boronic Acids with Cyclobutanone Ketoximes

AbstractIn this paper, an iron-catalyzed deboronation/cyanoalkylation of vinyl boronic acids for the preparation of distal cyanoalkyl alkenes with vinyl boronic acids as radical acceptor and activator is reported. In this reaction, various cyclobutanone oximes and substituted vinyl boronic acids can be transformed into the corresponding cyanoalkylated alkenes in moderate to good yields under these conditions. Mechanistic studies indicated that a single-electron transfer process may be involved in this transformation.

Alkylation of Glycine Derivatives through a Synergistic Single-Electron Transfer and Halogen-Atom Transfer Process.

Here, we present a versatile method for forming C(sp3)-C(sp3) bonds, enabling the synthesis of a range of natural and non-natural amino acids. This approach utilizes readily available glycine derivatives and alkyl iodides, combining single-electron transfer and halogen-atom transfer processes. The utility of this step-economic and redox-economic C(sp3)-C(sp3) bond formation is further highlighted in the late-stage site-selective modifications of the glycine residue in short peptides.

Light-Activated Nanocatalyst for Precise In-Situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

Triplet Energy Transfer (EnT)-Promoted 1,3-Dipolar Cycloaddition Reactions of N-(Trimethylsilyl)methylphthalimide with Electron-Deficient Alkynes and Alkenes.

Triplet energy transfer (EnT)-promoted photochemical pathways, arisen by visible light and its photosensitizers, have gained significant attention as a complementary strategy for initiating organic transformations in photochemical reactions that are unlikely to occur through a single electron transfer (SET) process. In the present study, we investigated the triplet EnT-promoted 1,3-dipolar cycloaddition reactions of N-(trimethylsilyl)methylphthalimide with electron-deficient alkynyl and alkenyl dipolarophiles. The triplet excited state of N-(trimethylsilyl)methylphthalimide, promoted by the triplet EnT from thioxanthone (TXA) photosensitizer, underwent sequential intramolecular SET and carbon-to-oxygen migration of the silyl group to form azomethine ylide. This generated ylide cycloadded to alkynes or alkenes to regioselectively and stereospecifically produce a nitrogen-containing benzopyrrolizidine scaffold with multiple stereogenic centers. Crucially, the stereoselectivity of these cycloaddition reactions (i.e., endo versus exo addition) was influenced by the nature of the dipolarophiles.

A universal molecular oxygen-mediated photocatalysis strategy to boost visible-light induced hydrogen evolution through partial water splitting

A universal oxygen-mediated, stepwise strategy is proposed for efficiently inducing visible-light photocatalytic partial water decomposition into hydrogen over various semiconductor photocatalysts with conduction band bottoms below the single-electron oxygen reduction potential. In this scenario, molecular O2 can be transformed into reactive oxygen species, serving as both an oxidant and a homogeneous catalyst for producing hydrogen from alkaline aqueous solution containing various organic substrates. Further enhancement the performance is achieved by doping with phosphorous and oxygen, which constructs a local internal electric field and introduces sulfur vacancies, thereby facilitating the transport of photogenerated charge carriers, particularly on a representative CdS photocatalyst. The optimal hydrogen evolution performance reaches 2321.4 and 8521.4 μmol·gcatatlyst−1·h−1 in methanol and formaldehyde solution systems, respectively, with an apparent quantum efficiency exceeding 59.4 % under 450 nm visible light irradiation. Mechanistic studies demonstrate that the oxygen-mediated, sequential single-electron transfer process can occur with virtually zero activation energy.

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.

Visible Light-Induced Electron-Donor-Acceptor-Mediated C-3 Coupling of Quinoxalin-2(1H)-ones with Unactivated Aryl Iodides.

Visible light-induced C-3 arylation of quinoxalin-2(1H)-ones with abundantly available aryl iodides with good yields via an electron-donor-acceptor (EDA)-complex formation have been accomplished. The radical scavenging, Electron paramagnetic resonance (EPR), UV-visible experiments, density functional theory (DFT), and quantum yield studies revealed that the reaction went through a radical pathway via a single electron transfer (SET) process. Furthermore, the protocol could also be applied to the synthesis of biologically active molecules, illustrating the practicality of the present protocol.

Photocatalyst-Free Visible Light-Induced C(sp2)-H Arylation of Quinoxalin-2(1H)-ones and Coumarins.

Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.

Cobalt Catalyzed α-Hydroxylation of Arylacetic Acid Equivalents with Dioxygen.

A cobalt catalyst, under oxidative conditions, facilitates the single electron transfer process in N-pyridyl arylacetamides to form α-carbon-centered radicals that readily react with molecular oxygen, giving access to mandelic acid derivatives. In contrast to the known benzylic hydroxylation approaches, this approach enables chemo- and regioselective hydroxylation at a benzylic position adjacent to (N-pyridyl)amides. Mild conditions, broad scope, excellent selectivity, and wide synthetic practicality set up the merit of the reaction.

Synergistic Copper-Aminocatalysis for Direct Tertiary α-Alkylation of Ketones with Electron-Deficient Alkanes.

In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules.

Catalytic Asymmetric Redox-Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3+2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol %), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclopentane rings involving an elusive but important all-carbon quaternary.