Involves Single-electron Transfer Research Articles

Selective C-N Bond Cleavage in Unstrained Pyrrolidines Enabled by Lewis Acid and Photoredox Catalysis.

Cleavage of inert C-N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage of the C-N bond in N-benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at the C2-N bond. Cyclic voltammetry and NMR studies demonstrated that the Lewis acid is crucial for promoting the single-electron transfer from the photoredox catalyst to the amide carbonyl group. This protocol is widely applicable to various pyrrolidine-containing molecules and enables inert C-N bond cleavage including C-C bond formation via intermolecular radical addition. Furthermore, the current protocol successfully converts pyrrolidines to aziridines, γ-lactones, and tetrahydrofurans, showcasing its potential of the inert C-N bond cleavage for expanding synthetic strategies.

Mechanistic insights into copper-mediated benzylic C(sp3)-H bond trifluoromethylation.

The mechanisms underlying copper-mediated trifluoromethylation of benzylic C(sp3)-H bonds were investigated using density functional theory (DFT) calculations. Two distinct pathways were identified: radical recombination/reductive elimination and single-electron transfer (SET). In the radical recombination/reductive elimination pathway, the CuII species recombines with benzyl radicals to generate a CuIII intermediate, which subsequently undergoes reductive elimination. Conversely, the SET pathway involves single-electron transfer from benzyl radicals to CuII species, forming a cationic benzylic intermediate and CuI species, followed by coupling with a CF3 group coordinated to Cu. DFT calculations revealed that the radical recombination/reductive elimination pathway is favoured for trifluoromethylation of primary and secondary benzylic C(sp3)-H bonds, with the reductive elimination step being rate-determining. In contrast, the SET pathway exhibits preference for trifluoromethylation of tertiary benzylic C(sp3)-H bonds. These mechanistic insights have significant implications for enhancing the selectivity of copper-mediated trifluoromethylation reactions.

Radical-Based Convergent Paired Electrolysis.

Electrochemistry offers a sustainable platform for discovering reactions involving single-electron transfer (SET) that generates highly reactive and synthetically versatile radical species. Compared with photochemistry similarly specializing in SET which requires expensive photocatalysts, electrochemistry employs low-cost electricity to drive the electron flow. Paired electrolysis makes use of both half-reactions, thus obviating the need for sacrificial reactions and maximizing the atom and energy economy. In convergent paired electrolysis, anodic oxidation and cathodic reduction occur simultaneously to generate two intermediates, which are then coupled to furnish the product. It represents a distinctive approach to challenging redox-neutral reactions. However, the gap between the two electrodes makes it hard for a reactive intermediate to come across the other coupling partner. This concept article summarizes recent state-of-the-art advances on radical-based convergent paired electrolysis, which adopted different strategies to overcome the difficulty.

Synthesis of BCP nitriles enabled by a metallaphotoredox-based multi-component reaction

In this issue of Chem Catalysis, Molander and co-workers develop a dual photoredox/nickel-catalyzed alkyl-, acyl-, and sulfonylcyanation of [1.1.1]propellane, providing a straightforward methodology for the synthesis of nitrile-substituted bicyclo[1.1.1]pentanes (BCPs). They propose a reaction pathway that involves single-electron transfer (SET) and reductive elimination.

Sc(OTf)3 catalyzed intramolecular single-electron transfer of 2-alkyl-1,4-benzoquinones: synthesis of 6-chromanols from donor-acceptor cyclopropanes.

A Sc(OTf)3 catalyzed intramolecular cyclization reaction of 2-alkyl-1,4-benzoquinone derived from D-A cyclopropane was discovered. This reaction involves single-electron transfer, proton-transfer, an aromatization driven spin center shift, and radical coupling processes, and offers an efficient method for the synthesis of 6-chromanols from D-A cyclopropanes.

Chromium-Catalyzed Cross-Coupling Reactions by Selective Activation of Chemically Inert Aromatic C–O, C–N, and C–H Bonds

AbstractTransition-metal-catalyzed cross-coupling has emerged as one of the most powerful and useful tools for the formation of C–C and C–heteroatom bonds. Given the shortage of resources of precious metals on Earth, the use of Earth-abundant metals as catalysts in developing cost-effective strategies for cross-coupling is a current trend in synthetic chemistry. Compared with the achievements made using first-row nickel, iron, cobalt, and even manganese catalysts, the group 6 metal chromium has rarely been used to promote cross-coupling. This perspective covers recent advances in chromium-catalyzed cross-coupling reactions in transformations of chemically inert C(aryl)–O, C(aryl)–N, and C(aryl)–H bonds, offering selective strategies for molecule construction. The ability of low-valent Cr with a high-spin state to participate in two-electron oxidative addition is highlighted; this is different from the mechanism involving single-electron transfer that is usually assigned to chromium-mediated transformations.1 Introduction2 Chromium-Catalyzed Kumada Coupling of Nonactivated C(aryl)–O and C(aryl)–N Bonds3 Chromium-Catalyzed Reductive Cross-Coupling of Two Nonactivated C(aryl)–Heteroatom Bonds4 Chromium-Catalyzed Functionalization of Nonactivated C(aryl)–H Bonds5 Conclusions and Outlook

Photoinduced Borylation for the Synthesis of Organoboron Compounds.

Organoboron compounds have important synthetic value and can be applied in numerous transformations. The development of practical and convenient ways to synthesize boronate esters has thus attracted significant interest. Photoinduced borylations originated from stoichiometric reactions of alkanes and arenes with well-defined metal-boryl complexes. Now, photoredox-initiated borylations, catalyzed by either transition metal or organic photocatalysts, and photochemical borylations with high efficiency have become a burgeoning area of research. In this Focus Review, we summarize research on photoinduced borylations, especially emphasizing recent developments and trends. This includes the photoinduced borylation of arenes, alkanes, aryl/alkyl halides, activated carboxylic acids, amines, alcohols, and so on based on transition metal catalysis, metal-free organocatalysis, and direct photochemical activation. We focus on reaction mechanisms involving single-electron transfer, triplet-energy transfer, and other radical processes.

Visible- and UV-Light-Induced Decarboxylative Radical Reactions of Benzoic Acids Using Organic Photoredox Catalysts.

Photoinduced decarboxylative radical reactions of benzoic acids with electron-deficient alkenes, diborane, and acetonitrile under organic photoredox catalysis conditions and mild heating afforded adducts, arylboronate esters, and the reduction product, respectively. The reaction is thought to involve single-electron transfer promoted the generation of aryl radicals via decarboxylation. A diverse range of benzoic acids were found to be suitable substrates for this photoreaction. Only our two-molecule organic photoredox system can work well for the direct photoinduced decarboxylation of benzoic acids.

Synergistic CO2 Mediation and Photocatalysis for α-Alkylation of Primary Aliphatic Amines

Recent work published by Rovis, Schoenebeck, and co-workers in Nature Chemistry describes a synergistic CO2 mediation and photocatalysis strategy for challenging α-alkylation of primary aliphatic amines by using quinuclidine as a hydrogen atom transfer (HAT) catalyst for γ-lactam synthesis. Electrostatic attraction between the in-situ-generated carbamate and quinuclidinium radical cation is critical for the selectivity.

Comparative study on the interactions of sulfide and iodine mediators with a dye in p-type dye-sensitized solar cells

The intermolecular interactions of a typical triphenylamine-based push-pull dye (P1) with three sulfide species T3−, T2, and T2− and with the iodine species I3−, I2, and I2− were investigated by means of density functional theory. The reduced form of P1 interacts with both T3− (I3−) and T2− (I2−) through reductive cleavage of the SS (II) bond, whereas T2 (I2) interactions involving single-electron transfer occur without SS (II) bond breakage. Therefore, regeneration with a thiolate–disulfide redox couple (as well as with iodide–triiodide) proceeds by three different mechanisms: by interaction with T3− (I3−) via the transient intermediate complex T2−⋯P1⋯T− (I2−⋯P1⋯I−) to give T2− (I2−) and T− (I−); by interaction with T2 (I2) via P1⋯T2− (P1⋯I2−) to give T2− (I2−); or by interaction with T2− (I2−) via T−⋯P1⋯ T− (I−⋯P1⋯I−) to give two T− (I−) moieties. The P1–T2− complexes have far fewer configurations, and the T2− species are much farther away from the semiconductor surface than are the I2− species in P1–I2−. This suggests that recombination of injected holes with electron donors in the thiolate–disulfide electrolyte is suppressed relative to that in iodide–triiodide, leading to a greater than expected increase in the open-circuit photovoltage for a p-type dye-sensitized solar cell.

Copper-Catalyzed Oxidative Carbon-Carbon and/or Carbon-Heteroatom Bond Formation with O2 or Internal Oxidants.

Selective oxidation, a fundamental organic transformation of critical importance, produces value-added products from simple organic molecules. This process is extensively used to incorporate heteroatoms into carbon-based molecules, where high-valent metal salts, hypervalent halogen reagents, and peroxides are widely used as oxidants. Oxidation reactions are extremely challenging because their selectivity is hard to control and/or they form significant quantities of unwanted waste derived from the stoichiometric oxidants. Undoubtedly, the utilization of green oxidants such as molecular oxygen (O2) or internal oxidants provides tunable oxidation abilities and produces no environmentally hazardous byproducts. Thus, synthetic chemists have devoted increasing attention to the utilization of green oxidants to obtain valuable products. Since the first industrial application of noble metal-catalyzed oxidation, i.e., Pd/Cu/O2-mediated Wacker oxidation, precious metal-catalyzed organic reactions have undergone significant development in both the laboratory and industry. However, the high cost and considerable toxicity of precious metals compel chemists to explore the catalytic activities of earth-abundant, first-row transition metals. Copper is abundant, easy to utilize, and relatively insensitive to water and air. Controllable access to Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states ensures that copper can be applied as a tunable and multifunctional catalyst. Copper-catalyzed transformations involve single-electron transfer (SET), two-electron processes (TEPs) and even the cooperation of SET and TEPs. More importantly, in Cu/O2 catalytic systems, ligands, additives, and solvents can tune the oxidation state of copper from Cu(I) to Cu(III). As a result, the development of copper-catalyzed aerobic oxidative reactions is possible and desirable. Progress in these synthetic methods will enable breakthroughs in natural product synthesis, materials science, and bioorganic chemistry. This Account describes our efforts over the last several years to develop copper-catalyzed C-C or C-heteroatom bond formation reactions with oxygen or internal oxidants as the oxidant. We primarily focused on reaction with simple substrates, including cross-couplings, cycloadditions, cyclizations, and condensations. These transformations provide convenient and efficient strategies for constructing multiple bonds, such as C-C/C-O bonds, C-C/C-N bonds, and C-N/C-S bonds, in one pot. Various alkynes, furans, benzofurans, lactones, sulfones, thioethers, and nitrogen-containing heterocyclic compounds were synthesized with high selectivity and atom economy from abundant, commercially available and inexpensive starting materials. These methods were successfully applied to the construction of drug molecules and skeletons of natural products. Additionally, the designed control experiments and serendipitous observations have given us mechanistic insights into copper-catalyzed green oxidation. Uncovering the activity of copper-catalyzed green oxidation involving oxygen and oxime esters has allowed us to extend the scope of those green oxidation reactions. We believe that copper-catalyzed green oxidation transformations can be made even more eco-friendly and economical in the synthesis of valuable compounds.

Elementary steps in electrical doping of organic semiconductors

Fermi level control by doping is established since decades in inorganic semiconductors and has been successfully introduced in organic semiconductors. Despite its commercial success in the multi-billion OLED display business, molecular doping is little understood, with its elementary steps controversially discussed and mostly-empirical-materials design. Particularly puzzling is the efficient carrier release, despite a presumably large Coulomb barrier. Here we quantitatively investigate doping as a two-step process, involving single-electron transfer from donor to acceptor molecules and subsequent dissociation of the ground-state integer-charge transfer complex (ICTC). We show that carrier release by ICTC dissociation has an activation energy of only a few tens of meV, despite a Coulomb binding of several 100 meV. We resolve this discrepancy by taking energetic disorder into account. The overall doping process is explained by an extended semiconductor model in which occupation of ICTCs causes the classically known reserve regime at device-relevant doping concentrations.

Cobalt-Catalyzed Directed Alkylation of Olefinic C–H Bond with Primary and Secondary Alkyl Chlorides

A cobalt–N-heterocyclic carbene catalytic system promotes pyridine-directed olefinic C–H alkylation reactions using a variety of primary and secondary alkyl chlorides under mild conditions. Radical clock experiments suggest that the reaction involves single-electron transfer from the cobalt intermediate to the alkyl chloride.

Cobalt-Catalyzed Chelation-Assisted Alkylation of Arenes with Primary and Secondary Alkyl Halides

Cobalt–N-heterocyclic carbene catalytic systems have been developed for chelation-assisted ortho-alkylation of aromatic compounds with alkyl halides. Aryl imines can be selectively monoalkylated at room temperature by various primary or secondary alkyl chlorides or bromides. The catalytic system can also be applied to 2-arylpyridine derivatives, which in the absence of steric hindrance are amenable to dialkylation by an excess of the alkyl halide. Mechanistic experiments, including reactions of stereochemical probes and radical clocks, indicate that the reaction involves single-electron transfer from the cobalt center to the alkyl halide to form the corresponding alkyl radical, which has a finite lifetime before it undergoes C–C bond formation.

Cobalt-catalyzed directed alkylation of arenes with primary and secondary alkyl halides

Abstract A cobalt–N-heterocyclic carbene catalyst allows ortho-alkylation of aromatic imines with unactivated primary and secondary alkyl chlorides and bromides under room-temperature conditions. The scope of the reaction encompasses or complements that of cobalt-catalyzed ortho-alkylation reactions with olefins as alkylating agents that we developed previously. Stereochemical outcomes of secondary alkylation reactions suggest that the reaction involves single-electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical. A cycloalkylated product obtained by this method can be transformed into unique spirocycles through manipulation of the directing group and the cycloalkyl groups.

Electron transferases.

The flavin isoalloxazine ring in electron transferases functions in a redox capacity, being able to take up electrons from a donor to subsequently deliver them to an acceptor. The main characteristics of these flavoproteins, including their unique ability to mediate obligatory processes of two-electron transfers with those involving single-electron transfer, are here described. To illustrate the versatility of these proteins, the acquired knowledge of the function of the two electron transferases involved in the cyanobacterial photosynthetic electron transfer from photosystem I to NADP(+) is presented. Many aspects of their biochemistry and biophysics have been extensively characterized using site-directed mutagenesis, steady-state and transient kinetics, spectroscopy, calorimetry, X-ray crystallography, electron paramagnetic resonance, and computational methods.

Cobalt-Catalyzed Ortho Alkylation of Aromatic Imines with Primary and Secondary Alkyl Halides

We report here cobalt-N-heterocyclic carbene catalytic systems for the ortho alkylation of aromatic imines with alkyl chlorides and bromides, which allows the introduction of a variety of primary and secondary alkyl groups at room temperature. The stereochemical outcomes of the reaction of secondary alkyl halides suggest that the present reaction involves single-electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical. A cycloalkylated product obtained by this method can be transformed into unique spirocycles through manipulation of the directing and cycloalkyl groups.

Copper-Catalyzed Oxaziridine-Mediated Oxidation of C–H Bonds

The highly regio- and chemoselective oxidation of activated C-H bonds has been observed via copper-catalyzed reactions of oxaziridines. The oxidation proceeded with a variety of substrates, primarily comprising allylic and benzylic examples, as well as one example of an otherwise unactivated tertiary C-H bond. The mechanism of the reaction is proposed to involve single-electron transfer to the oxaziridines to generate a copper-bound radical anion, followed by hydrogen atom abstraction and collapse to products, with regeneration of the catalyst by a final single-electron transfer event. The involvement of allylic radical intermediates was supported by a radical-trapping experiment with TEMPO.

Generation of the ArCF22+ Dication

Thermal reactions of the CF32+ dication with argon lead to the formation of an ArCF22+ dication, a new type of metastable species with an argon−carbon bond. None of the other rare gases undergo a similar reaction with CF32+. For the lighter rare gases (He and Ne), no reactions with CF32+ other than those due to electronically excited reactant ions are observed, whereas for the heavier rare gases (Kr and Xe), the prevailing reactive pathways involve single-electron transfer. At elevated collision energies, single-electron transfer predominates for collisions with all rare gases (He−Xe).

Boomerang‐Type Substitution Reaction: Reactivity of Fullerene Epoxides and a Halofullerenol

The C(s)-symmetric fullerene chlorohydrin C60(Cl)(OH)(OOtBu)4 reacts with 4-dimethylaminopyridine (DMAP) and 1,4-diazabicyclo[2.2.2]octane (DABCO) to yield two isomers with the formula C60(O)(OOtBu)4 in good yields. These isomers differ with respect to the location of the epoxy functionality. The one from DMAP is C(s) symmetric, whereas that from DABCO is C1 symmetric with the epoxy group on the central pentagon. Two different mechanisms are proposed to explain the chemoselectivity of these reactions. The reaction with DMAP involves single-electron transfer as the key step; DMAP acts as the electron donor. A combination of an oxygen-atom shift and S(N)2'' processes (boomerang substitution) are responsible for the formation of isomer with DACBO. Various related reactions support the proposed mechanisms. The structures of new fullerene derivatives were determined by spectroscopy, single-crystal X-ray analysis, and chemical correlation experiments.