Radical Reactions Research Articles

Dietary ferulic acid supplementation enhances antioxidant capacity and alleviates hepatocyte pyroptosis in diquat challenged piglets

BackgroundOxidative stress significantly impacts growth performance and liver function in piglets. Ferulic acid (FA) works as an antioxidant, however, the role and mechanism of FA in the regulation of diquat-induced oxidative stress in piglets are less known. This study was designed to investigate the effects of FA on growth performance and antioxidant capacity in piglets with diquat challenge.MethodsThirty-two healthy DLY (Duroc × Landrace × Yorkshire) piglets (13.24 ± 0.19 kg) were randomly divided into one of two diets including 0 or 4 g/kg FA for 14 d. On d 15, all pigs were intraperitoneally injected diquat or sterile saline.ResultsDietary supplementation with ferulic acid (FA) significantly improved the average daily gain (ADG) and decreased feed-gain ratio (F/G) of piglets. Here, dietary FA supplementation reduced serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities in diquat challenged piglets. Furthermore, diquat infusion increased reactive oxygen radicals (ROS) level in liver, decreased the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and increased malondialdehyde (MDA) content in the liver and serum. Supplementation with FA significantly increased T-AOC and T-SOD activities and decreased MDA and ROS levels. FA down-regulated gene and protein expression of Keap1, and up-regulated protein expression of Nrf2 and HO-1 in the liver of piglets with diquat challenge. Importantly, diquat challenge increased the ratio of late apoptosis, increased serum levels of IL-1β, IL-18 and lactate dehydrogenase (LDH), and up-regulated pyroptosis-related genes in the liver. FA supplementation reduced the ratio of late apoptosis and down-regulated mRNA expression of Caspase-1. Accordingly, FA addition reduced concentration of IL-1β, IL-18, and LDH under diquat challenge.ConclusionsDiquat-induced oxidative stress reduced growth performance and impaired liver function in piglets. Dietary FA supplementation enhanced the antioxidant capacity and reduced the degree of hepatocyte pyroptosis, thereby alleviating the oxidative damage in the liver and mitigating the impact of diquat on growth performance of piglets.

Radical reactions for reversible click chemistry

Radical reactions for reversible click chemistry

C-H Functionalization of Poly(ethylene oxide) - Embracing Functionality, Degradability, and Molecular Delivery.

This study presents an organocatalytic C-H functionalization approach for postpolymerization modification (PPM) of poly(ethylene oxide) (PEO). Most of PEO PPM is previously processed at the end hydroxy group, but recent advances in C-H functionalization open a way to modify the backbone position. Structurally diverse carboxylic acids are attached to PEO through a cascade process of radical generation by peroxide and oxidation to oxocarbenium by tertiary butylammonium iodide. Attaching carboxylic acids yields a series of functionalize PEO with acetal units (2-5 mol%) in a backbone, which is not accessible via conventional copolymerization of epoxides. The optimized conditions minimizes the uncontrolled degradation or crosslinking from the highly reactive radical and oxocarbenium intermediate. The newly introduced acetal units bring degradability of PEO as well as delivery of carboxylic acid molecules. Hydrolysis studies with high molecular weight functionalization PEO (Mn = 13.0kgmol-1) confirm the steady release of fragmented PEO (Mn ∼ 2.0kgmol-1) and carboxylic acid over days and the process rate is not sensitive to pH variation between pH 5 and 9. The presented method offers a versatile and efficient way to modify PEO with potential energy and medical applications.

Radical Reactions with Chiral Acylammonium Salts: Synthesis of Functionalized δ-Lactams through Giese-Initiated Organocascades.

Enantioselective Giese reactions employing chiral α,β-unsaturated acylammonium salts and subsequent diastereoselective trapping followed by lactamization deliver optically active δ-lactams. Alkyl iodides bearing tosylamides undergo radical initiation using triethylborane at low temperatures to provide carbon-centered radicals to initiate the described organocascade. Subsequent diastereoselective inter- or intramolecular trapping of the incipient α-radical leads to highly functionalized, enantioenriched mono- and bicyclic δ-lactams (up to 99:1 er, > 19:1 dr) bearing up to three stereogenic centers. Interestingly, benzotetramisole imparts diastereoselectivity that contradicts steric considerations alone. Results from DFT calculations rationalized the observed enantio- and diastereoselectivities, revealed an electrostatic interaction between the sulfone oxygens and the ammonium cation in the initial α-radical intermediate, and aided in application of this methodology to bicyclic δ-lactams through intramolecular trapping of the α-radical intermediate.

Improved body and interface properties of EPDM insulation for HVDC cable accessory by grafted voltage stabilizer

As a key component in HVDC cable accessory, EPDM insulation is prone to breakdown both in body and along interface. To improve the comprehensive electrical strength of EPDM, voltage stabilizer 2-propenyl-4,6-dibenzoylresorcinol (ADR) was simultaneously grafted onto macromolecules through free radical reaction on its vinyl during crosslinking of EPDM. After modification, the mechanical strength and thermal stability of EPDM are improved. In terms of body properties, the injection and rapid transfer of space charge under normal electric field are weakened, the volume conductivity is reduced, the breakdown strength is improved and the growth of electrical tree is suppressed. In terms of interface properties, the normal electric field at the EPDM/XLPE interface is weakened, hence reduced potential risk of deterioration initiated from interface. Moreover, the surface conductivity of EPDM is reduced, the charge accumulation and migration along the EPDM/XLPE interface are suppressed, and the interface breakdown strengths under different interface pressures are significantly increased under tangential electric field. Molecular simulations and UV absorption characteristics indicate that the grafted ADR molecules not only introduce charge traps into EPDM, but also absorb the high energy from trapped electrons and consume it through multiple excitations, thus preventing the electron avalanche and subsequent degradation of EPDM.

Silver-Catalyzed 1,2-Thiosulfonylation of Alkenes: Development of a Nucleophilic d3-Methylthiolating Reagent.

Development of robust d3-methylthiolating reagents represents an attractive synthetic method to access deuterated molecules in the field of drug discovery. Here, we report a straightforward strategy to prepare electrophilic S-methyl-d3 arylsulfonothioates in one-step without column purification. These reagents exhibit good radical reactivity toward silver-catalyzed vicinal thiosulfonylation of alkenes or 1,6-enynes on water. As a result, simultaneous incorporation of both SCD3 and ArSO2 units into unsaturated carbon-carbon bonds with 100% atom economy has been established. Moreover, the ATRA adducts with >99% D incorporation can serve as nucleophilic d3-methylthiolating synthons via retro-Michael addition under mild basic conditions, providing a good alternative in trideuteromethylthiolating alkyl iodides to access corresponding trideuteromethyl sulfides with high efficiency.

Radical Polarity.

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence and predict its effects, the electrophilicity/nucleophilicity of >500 radicals has been calculated. This database of open-shell species entails frequently encountered synthetic intermediates, including radicals centered at sp3, sp2, and sp hybridized carbon atoms or various heteroatoms (O, N, S, P, B, Si, X). Importantly, these computationally determined polarities have been experimentally validated for electronically diverse sets of >50 C-centered radicals, as well as N- and O- centered radicals. High correlations are measured between calculated polarity and quantified reactivity, as well as within parallel sets of competition experiments (across different radical types and reaction classes). These multipronged analyses show a strong relationship between the computed electrophilicity, ω, of a radical and its relative reactivity (krel vs Δω slopes up to 40; showing mere Δω of 0.1 eV affords up to 4-fold rate enhancement). We expect this experimentally validated database will enable reactivity and selectivity prediction (by harnessing polarity-matched rate enhancement) and assist with troubleshooting in synthetic reaction development.

Revealing the Intrinsic Correlation between Cu Scales and Free Radical Chain Reactions in the Regulation of Catalytic Behaviour.

Defining the copper-based catalysts that are responsible for the catalytic behaviour of oil-paper insulation systems and implementing effective regulation are of great significance. Accelerated ageing experiments were conducted to reveal variations in copper scales and deterioration in insulation properties. As ageing progressed, TEM images demonstrated that copper species were adsorbed and aggregated on the fibre surface in the form of nanoparticles (NPs). The scale of NPs exhibited a continuous increase, from 27.06 nm to 94.19 nm. Cu(I) and Cu(II) species were identified as the active sites for inducing intense free radical reactions, which significantly reduced the activation energy, making the insulating oil more susceptible to oxidation. The role of the antioxidant di-tert-butyl-p-cresol (DBPC) in extending the insulation life was regulated by determining the optimal addition time based on variations in the interfacial tension. After the second addition of DBPC, the ageing rates of the dissipation factor, acidity, micro-water and breakdown voltage in the Cu+DBPC group decreased by 28.8%, 43.2%, 52.9% and 46.7%, respectively, compared to the Cu group. This finding not only demonstrates the crucial role of DBPC in preventing the copper-based catalyst-induced oxidation of insulating oil, but also furnishes a vital foundation for enhancing the long-term stability of transformer insulation systems.

Using Er/Cd-Codoped Bi4O5Br2 Microspheres to Enhance Antibiotic Degradation under Visible Illumination: A Combined Experimental and DFT Investigation.

High levels of antibiotic accumulation and the difficulty of degradation can have serious consequences for the environment and, therefore, require urgent attention. To solve this problem, a synergistic Er and Cd ion-codoped Bi4O5Br2 photocatalyst was proposed. The degradation rate of sulfamethoxazole (SMX) by Er/Cd-Bi4O5Br2 was eight times higher than that of pure Bi4O5Br2, exceeding that of single Er-doped or Cd-doped Bi4O5Br2, which was attributed to the ability of Er/Cd-Bi4O5Br2 to generate a variety of free radicals. Experimental results and theoretical calculations suggested a possible mechanism for the improved photocatalytic degradation rate. The reduction of the band gap can facilitate the production of electron-hole pairs, which play a significant role in the production of reactive radicals. Furthermore, an optimal stabilized structure of the ErCd-Bi4O5Br2 dopant system was identified based on the formation energy formulas of different ligand configurations. These findings offer promising potential for the degradation of broad-spectrum antibiotics and provide valuable insights for the design and modification of photocatalytic materials.

Selective Functionalization of Alkenes and Alkynes by Dinuclear Manganese Catalysts.

ConspectusAlkenes and alkynes are fundamental building blocks in organic synthesis due to their commercial availability, bench-stability, and easy preparation. Selective functionalization of alkenes and alkynes is a crucial step for the synthesis of value-added compounds. Precise control over these reactions allows efficient construction of complex molecules with new functionalities. In recent decades, second- and third-row precious transition metal catalysts (palladium, platinum, rhodium, ruthenium) have been pivotal in the development of metal-catalyzed synthetic methodology. These metals exhibit excellent catalytic activity and selectivity, enabling efficient synthesis of functionalized organic molecules. However, recovery and reuse of precious metals have long been a challenge in this field. In recent years, exploration of earth-abundant metal-catalyzed organic reactions has interested both academic and industrial researchers. The development of such catalytic systems offers a promising approach to overcome the limitations of precious metal catalysts. For example, manganese is the third most naturally abundant transition metal with minimal toxicity and excellent biocompatibility. It exhibits good catalytic activity in several organic reactions, including C-H bond functionalization, selective reduction, and radical reactions. This Account outlines our recent progress in dinuclear manganese catalysis for selective functionalization of alkenes and alkynes. We have established the elementary manganese(I)-catalysis in transmetalation with R-B(OH)2. This finding has enabled us to apply the catalyst for the selective 1,2-difunctionalization of structurally diverse alkenes and alkynes. Mechanistic studies suggest a double manganese center synergistic activation model, as superior to Mn(CO)5Br in some cases. In addition, we have developed a ligand-tuned metalloradical strategy of dinuclear manganese catalysts (Mn2(CO)10), bridging the gap between the organometallics and radical chemistry, highlighting the unique radical functionalization of alkenes. Interestingly, using the same starting materials, different ligands can deliver completely different products. Meanwhile, a cooperative catalysis strategy involving manganese and other catalysts (e.g., cobalt, iminium) has also been developed and is briefly discussed. For manganese/iminium synergistic catalysis, a new mechanism for migratory insertion and demetalization-isomerization in synergistic HOMO-LUMO activation was disclosed. This strategy expands the application of low-valent manganese catalysts for enantioselective C-C bond-forming reactions. New reaction discovery is outpacing mechanism studies for dinuclear manganese catalysis, and future studies with time-resolved spectroscopy will improve understanding of the mechanism. Based on these intriguing findings, the precise functionalization of alkenes and alkynes by dinuclear manganese catalysts will expedite a novel activation model to enable late-stage functionalization of complex molecules.

Manganese-Catalyzed Cycloalkene Ring Expansion Synthesis of Azaheterocycles.

Herein, a Mn catalytic protocol has been developed for the cycloalkene ring expansion synthesis of azaheterocycles, allowing broad-substrate-scope access to pyridine and isoquinoline derivatives. The initial monoaddition of an azidyl radical to alkene and further as-generated C-radical addition to O2, followed by intramolecular rearrangement and aromatization, showcase a distinct Mn-catalyzed radical reactivity mode. The reaction features a short reaction time and a broad substrate scope, with applications demonstrated in complex structure elaboration and gram-scale vismodegib synthesis.

Modification of activated carbon through chemical-physical activation method with KOH and 60Co gamma irradiation from banana leaf waste

Abstract Until now waste is still a problem in many big cities in Indonesia. In addition, the amount of waste increases as the population increases. Banana leaf waste is no exception, which is included in other types of waste, which accounts for 6.33% of the total waste in Indonesia in 2022. Utilization of banana leaf waste as a raw material for activated carbon production can also be an alternative to reducing the amount of wasted banana leaf waste because they contain various kinds of organic compounds. Activated carbon is widely used as an adsorbent in various sectors, especially in the industrial sector. Production of activated carbon must go through an activation process to enlarge the surface pores either chemically or physically, or even both. This study aims to compare the results of activated carbon surface area and functional groups using the chemical-physical activation method from banana leaf biomass raw materials with KOH and gamma irradiation at various doses. The research method used is an experimental method consisting of 4 stages: dehydration, carbonization, activation, and characterization. The research was started by dehydrating the leaves and continued with the carbonization stage at 350°C for 30 minutes. Carbon was divided into four samples that consisted of 1 blank and 3 test materials that activated with 30% (w/v) KOH solution for 24 hours and gamma-irradiated with a dose of 10, 30, and 50 kGy. Results were characterized using FTIR and BET. The effect of gamma 60Co irradiation on the activated carbon material from banana leaf waste can increase the peak transmittance value of the activated carbon functional group due to the formation and reaction of free radicals on its surface. Increase in the surface area (from 6.504 to 24.04 m2/g) is also associated with an increase in the absorbed dose due to the formation of more free radicals. However, the surface area obtained is not as expected due to the possibility of pore blockage and excessive activation time, which causes the surface area of the material to be small.

Antioxidant Activity of Gold Nanofilms Synthesized via Cyclic Voltammetry Technique

Abstract Gold nanoparticles (AuNPs) have attracted much attention as one of the most effective agents with high catalytic activities for radical scavenging reactions. Many studies have investigated its antioxidant activity using various in vitro methods and have shown promising scavenging action. In this research, we demonstrated the synthesis of Au nanofilms (AuNFs) by cyclic voltammetry technique and evaluated for their antioxidant activity. The application of a range of voltage levels was utilized in the synthesis of AuNFs, and their antioxidant potential was subsequently assessed through in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. All AuNFs exhibited antioxidant activity which increased as the upper potential was reduced from 1,5 V to 0,75 V. The antioxidant activity of AuNFs was shown to increase gradually with longer incubation times before the DPPH assay, indicating a significant impact on their performance. The obtained inhibition percentage was ranging from 8,26% to 22,91%. The highest antioxidant activity could be achieved by synthesizing AuNFs using 0,75V of upper potential and incubating it for 90 minutes prior to DPPH assay. The variations in the applied potential influenced the morphological characteristics of AuNFs, leading to increased surface area, while the duration of incubation was found to enhance the efficacy of the scavenging reaction between the AuNFs and DPPH. In conclusion, this cyclic voltammetry technique was shown to successfully synthesize AuNFs with significant antioxidant activity.

Photoredox decarboxylative acylation of carboxylic acid by 4-acyl-1,2,3-triazoliums

Recent advancements in NHC-based radical coupling reactions have introduced NHC-derived ketyl radicals as innovative persistent radicals. However, current work involves NHC-based radical-radical coupling reactions that are limited to some stable alkyl radicals of the radical partners. This is mainly due to the high barriers among the transition state in the coupling process. Our study, supported by density functional theory (DFT) calculations, demonstrates that ketyl radicals derived from mesoionic carbenes (MICs) exhibit significantly lower barriers for radical-radical coupling. This facilitates rapid reactions with short-lived alkyl radicals. Herein, we disclose 4-acyl-1,2,3-triazoliums as versatile acylation reagents, which can be converted to MIC-derived ketyl radicals by photocatalyst. Photoredox decarboxylative acylation of primary, secondary, and tertiary carboxylic acids afford the corresponding ketones with broad substrate scope and excellent functional group tolerance.

Maleimide-induced crosslinking of polyimide membranes for high gas separation performance and plasticization resistance

Trade-off effect and plasticization are the key issues confronted in the area of membrane separation when dealing with applications involving high-pressure, soluble gases like CO2. In this study, a novel diamine (TAPA-MAA) was synthesized derived from tris(4-aminophenyl)amine (TAPA) and maleic anhydride (MA). This diamine was copolymerized with DAM (2,4,6-trimethylbenzene-1,3-diamine) and 6FDA (4,4′-(hexafluoroisopropylidene)diphthalic anhydride) to form the polyimide (PI) membrane containing maleimide (MI) cross-linking sites via chemical imidization way. Then, under the action of heat treatment, the crosslinked PI (cPI) membrane was constructed since the MI crosslinking initiates a radical cycloaddition reaction to form a succinimide-linked structure, and named as cPSI membrane for short. Further, an increase in the ratio of TAPA-MAA gives rise to the resultant cPSI membrane with elevated cross-linking density. The obtained cPSI membranes showed significantly enhanced gas selectivities and superior anti-plasticization property compared to the un-crosslinked PI membranes due to the MI-induced crosslinking reaction in the PI main chain, resulting in a marked increment (24 %) in ultra-microporosity (<7 Å) and a reduction in the d-spacing value (6.10 Å vs 5.80 Å), generating a strong molecular sieving effect. Meanwhile, the highly interconnected covalent structure formed by the MI-induced crosslinking will suppress the plasticizing phenomenon induced by high-pressure soluble gases. The typical membrane (cPSI-3:7-350) possessed great CO2/CH4 separation performance, CO2 permeability of 334.4barrer and a CO2/CH4 selectivity of 61.9 that is exceeded the 2008Roberson upper bound, along withCO2 plasticization pressures above 44 bar. Besides, its mixed CO2/CH4 separation performance exceeded the 2018 upper gas mixture limit when the upstream pressure changed from 2-20 bar. This study provides valuable insights for the design of PIs containing MI cross-linking sites, which can enhance the performance of membrane-based gas separation.

Novel Catalyst-free Activation of Chlorine by Visible Light for Micropollutant Abatement

This study systematically investigated the direct activation of chlorine by visible light emitting diode (Vis-LED). Vis-LED could effectively activate chlorine to degrade micropollutants with degradation efficiency and pseudo-first-order degradation rate constant range of 64.3%-100% and 0.0340-0.195min-1, respectively. Quenching experiments and modeling results suggested that reactive chlorine species (RCS, including ClO•, Cl2•-, and Cl•) and hydroxyl radical (•OH) were involved in the degradation of atenolol (ATL). The contribution ratio of ClO•, free available chlorine, Cl•, Cl2•-, and •OH to ATL degradation were 58.7%, 17.4%, 15.6%, 1.8%, and 5.9%, respectively, in Vis-LED448/chlorine process. Moreover, the innate quantum yields of HClO and ClO- decreased from 0.229 and 0.0206 to 0.0489 and 0.0109mol·Einstein-1, respectively, as the wavelength increased from 448 to 513nm, leading to a decrease in ATL degradation, which was consistent with the model results. Experimental and modeling results have confirmed that ATL degradation decreased when pH increased from 4.0 to 9.0. Cl- had little effect on the degradation of ATL, while HA and HCO3- affected ATL degradation by scavenging reactive species and/or shielding effect. The concentration of disinfection by-products decreased with the increase of wavelength and pH. In summary, Vis-LED/chlorine is an efficient water treatment process even without a catalyst.

Photodegradation of RB5 dye with modified zeolites: influence of temperature and UV irradiation

Abstract This study explores the photocatalytic degradation of Reactive Black 5 (RB5) dye using thermally modified natural zeolites, aiming to improve water purification methods. Zeolites were calcined at 250 °C, 350 °C, and 500 °C, and characterized through x–ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR) to analyze their structural and morphological transformations. The results reveal that calcination significantly enhances the photocatalytic performance, particularly for ZNM500, which exhibited the highest efficiency, reaching a 60% removal rate of RB5. The degradation process follows a pseudo-first-order kinetic model at lower dye concentrations but adheres more closely to the Langmuir–Hinshelwood equation at higher concentrations, emphasizing the role of surface adsorption in catalysis. UV irradiation was a key factor in boosting reaction rates, with shorter wavelengths (254 nm) providing greater energy, leading to more effective dye breakdown by facilitating the generation of reactive hydroxyl radicals (·OH). These findings suggest that thermally modified zeolites, especially ZNM500, represent a promising solution for wastewater treatment, offering an efficient, cost–effective, and environmentally friendly approach to removing synthetic dyes from contaminated water sources.

The reverse-reduction effect of dissolved organic matter on the degradation of micropollutants induced by halogen radicals (Cl2•- and Br2•-)

Reactive halogen radicals (e.g., Cl2•- and Br2•-) greatly impact the degradation of micropollutants in natural waters and engineered water treatment systems. The ubiquitous dissolved organic matter (DOM) in real waters is known to greatly inhibit the degradation of micropollutants by reducing micropollutant's intermediate (i.e., TC•+/TC(-H)•), however, such DOM's effects on the halogen-radical-induced system have not been understood yet. The present study focuses on investigating and quantifying such inhibitory effects of DOM during Cl2•-- and Br2•--mediated process. Guanosine (Gs) was selected as a model compound. The transient spectra show that Cl2•- and Br2•- react with Gs generating intermediates (i.e., Gs•+/Gs(-H)•) via single-electron transfer. In the presence of 1.0 mgCL-1 DOM, over 70% of this oxidized Gs was reduced back to Gs. Comparing the extent of reverse-reduction inhibitory among different reaction systems, this inhibitory in Br2•- system was slightly lower than that in Cl2•- and SO4•- system, corresponding the slightly difference of inhibition factor (IF) values as SO4•- < Cl2•- < Br2•-. The reverse-reduction effect of DOM was further quantified for 19 common micropollutants. It varied significantly with IF values of 0.21–1.26 and 0.28–1.40 in Cl2•-- and Br2•--mediated process, respectively. Purines and amines generally exhibited more pronounced inhibition than phenols in both systems. A good correlation of IF values with micropollutant's reduction potential was observed, which can be applied to predict the degradation of more unstudied micropollutants. This study highlights the important role of the reverse-reduction effect of DOM on micropollutant degradation. It can significantly improve the accuracy in predicting degradation rate in advanced oxidation processes for treating water containing halides.

Enhancing marine protection: Antibacterial, anti-corrosion, and wettability properties of smart coatings via magnet assisted jet electrodeposition

Marine biofouling poses significant challenges to marine infrastructure. Current marine antifouling coatings face issues such as long-term stability, non-toxicity, and cost-effectiveness. This study investigates the preparation of smart coatings using nano-ZrO2/Ni composite materials via magnet assisted jet electrodeposition, varying the concentration of ZrO2 nanoparticles. The coatings’ structure and surface morphology were analyzed, and their antibacterial, anti-corrosion, and wettability properties evaluated. The results showed that the smart coatings were hydrophobic and could generate reactive oxygen species radicals, and the use of magnetic field preparation also resulted in a microscopic raised structures on the surface, with an antibacterial effect that exceeded that of pure nickel coatings. Increasing the concentration of ZrO2 nanoparticles enhanced coating density and significantly improved anti-corrosion properties. The composition distribution of Zr was the most homogeneous when the mass concentration of ZrO2 nanoparticles was 4 g/L. The development of smart coatings presents promising potential for combating marine biofouling, offering enhanced protection and application prospects in marine environments.

Cooperative NHC and Photoredox Catalyzed Radical Aminoacylation of Alkenes to Tetrahydropyridazines.

Tetrahydropyridazines constitute an important structural motif found in numerous natural products and pharmaceutical compounds. Herein, we report an aminoacylation reaction of alkenes that enables the synthesis of 1,4,5,6-tetrahydropyridazines through cooperative N-heterocyclic carbene (NHC) and photoredox catalysis. This approach involves the 6-endo-trig cyclization of N-centered hydrazonyl radicals, generated via single-electron oxidation of hydrazones, followed by a radical-radical coupling step. The mild process tolerates a wide range of common functional groups and affords a variety of tetrahydropyridazines in moderate to high yields. Preliminary investigations using chiral NHC catalysts demonstrate the potential of this protocol for asymmetric radical reactions.