Reactive Intermediates Research Articles

MiRNAs Involvement in Modulating Signalling Pathways Involved in Ros-Mediated Oxidative Stress in Melanoma.

Reactive oxygen species (ROS) are intermediates in oxidation-reduction reactions with the capacity to modify biomolecules and temporarily or permanently alter cell behaviour through signalling pathways under physiological and pathophysiological conditions where there is an imbalance between oxidative factors and the antioxidant response of the organism, a phenomenon known as oxidative stress. Evidence suggests that the differential modulation of ROS-mediated oxidative stress occurs in the pathogenesis and progression of melanoma, and that this imbalance in redox homeostasis appears to be functionally linked to microRNA (miRNA o miRs)-mediated non-mutational epigenetic reprogramming involving genes and transcription factors. The relationship between ROS-mediated stress control, tumour microenvironment, and miRNA expression in melanoma is not fully understood. The aim of this review is to analyse the involvement of miRNAs in the modulation of the signalling pathways involved in ROS-mediated oxidative stress in melanoma. It is hoped that these considerations will contribute to the understanding of the mechanisms associated with a potential epigenetic network regulation, where the modulation of oxidative stress is consolidated as a common factor in melanoma, and therefore, a potential footprint poorly documented.

Practical Considerations for Understanding Surface Reaction Mechanisms Involved in Heterogeneous Catalysis.

Acquiring useful knowledge about the active site(s) of a catalyst, nature of reactant-catalyst interactions, nature of reactive intermediates, rate-determining step, reaction rate orders that affect various process parameters, and reaction mechanism as a whole is exceedingly challenging. This is especially true in the case of heterogeneous catalysts due to the complexity of the nature of surface active sites and their nonstatic behavior. Here, we present our perspective on differentiating between various surface reaction mechanisms in light of pioneering studies by leaders in the field, with the aim of clarifying some of the confusion associated with these complex mechanisms, especially the Eley-Rideal mechanism. Using bibliometric analysis, we identify and discuss the following four reactions that most commonly invoke the Eley-Rideal mechanism: H2 activation, CO oxidation, esterification of alcohols by acids, and selective catalytic reduction (SCR) of NO x with NH3. Our analysis of studies utilizing well-suited experimental and computational methodologies for differentiating surface reaction mechanisms suggests that the above-mentioned four reactions do not occur via the Eley-Rideal mechanism. Instead, each reaction occurs via the Langmuir-Hinshelwood mechanism with nonidealities present. Lastly, we highlight practical considerations regarding select experimental (characterization methods and differential kinetics) and computational modeling that we believe can provide useful insights to accurately discern between the various possible reaction mechanisms in heterogeneous catalysis.

Surface Structure and Chemistry of CeO2 Powder Catalysts Determined by Surface-Ligand Infrared Spectroscopy (SLIR).

ConspectusCerium is the most abundant rare earth element in the Earth's crust. Its most stable oxide, cerium dioxide (CeO2, ceria), is increasingly utilized in the field of catalysis. It can catalyze redox and acid-base reactions, and serve as a component of electrocatalysts and even photocatalysts. As one of the most commonly used in situ/operando characterization methods in catalysis, infrared (IR) spectroscopy is routinely employed to monitor reaction intermediates on the surface of solid catalysts, offering profound insight into reaction mechanisms. Additionally, IR vibrational frequencies of probe molecules adsorbed on solid catalysts provide detailed information about their structure and chemical states. Numerous studies in the literature have utilized carbon monoxide and methanol as IR probe molecules on ceria particles. However, assigning their vibrational frequencies is often highly controversial due to the great complexity of the actual surface of ceria particles, which include differently oriented crystal facets, reconstructions, defects, and other structural variations. In our laboratory, taking bulk ceria single crystals with distinct orientations as model systems, we employed a highly sensitive ultrahigh vacuum (UHV) infrared spectroscopy system (THEO) to study the adsorption of CO and methanol. It turns out that the theoretical calculations adopting hybrid functionals (HSE06) can bring the theoretical predictions into agreement with the experimental results for the CO frequencies on ceria single crystal surfaces. The obtained frequencies serve as reliable references to resolve the long-standing controversial assignments for the IR bands of CO and methanol adsorbed on ceria particles. Furthermore, these characteristic frequencies allow for the determination of orientations, oxidation states and restructuring of exposed crystal facets of ceria nanoparticles, which is applicable from UHV conditions to industrially relevant pressures of up to 1 bar, and from low temperatures (∼65 K) to high temperatures (∼1000 K). We also used molecular oxygen as a probe molecule to investigate its interaction with the ceria surface, crucial for understanding ceria's redox properties. Our findings reveal that the localization of oxygen vacancies and the mechanism of dioxygen activation are highly sensitive to surface orientations. We provided the first spectroscopic evidence showing that the oxygen vacancies on ceria (111) surfaces tend to localize in deep layers. In addition, we employed N2O as a probe molecule to elucidate the origin of the photocatalytic activity of ceria and showed that the photocatalytic activity is highly sensitive to the surface orientation (i.e., surface coordination structure). This Account shows that probe-molecule infrared spectroscopy serves as a powerful in situ/operando tool for studying the surface structure and chemistry of solid catalysts, and the knowledge gained through the "Surface Science" approach is essential as a crucial benchmark.

Next‐Generation Time‐Resolved Electron Paramagnetic Resonance for Direct Visualizing Mechanisms in Radical Chemistry

AbstractRadical chemistry is an important research field that plays a vital role in life science, material science, and energy conversions. However, directly visualizing the transient open‐shell intermediates unambiguously in radical chemistry is a significant and long‐standing challenge. Recently, we have developed an innovative ultrawide single‐sideband phase‐sensitive detection (U‐PSD) time‐resolved electron paramagnetic resonance (TREPR) technique, which enables the characterization of diverse transient radical intermediates and mechanistic studies close to reaction conditions. In this brief review, we will offer an outline of the principles underlying our U‐PSD TREPR technique, and present examples highlighting the technique's ability to accurately characterize and track free radical intermediates in photocatalytic reactions.

Accelerated Indirect Photodegradation of Organic Pollutants at the Soil-Water Interface.

Indirect photolysis driven by photochemically produced reactive intermediates (PPRIs) is pivotal for the transformations and fates of pollutants in nature. While well-studied in bulk water, indirect photolysis processes at environmental interfaces remain largely unexplored. This study reveals a significant acceleration of indirect photodegradation of organic pollutants at the soil-water interface of wetlands. Organic pollutants experienced ubiquitously enhanced indirect photodegradation at the soil-water interfaces, with rates 1.41 ± 0.01 to 4.27 ± 0.03-fold higher than those in bulk water. This enhancement was observed across various natural and artificial wetlands, including coastal wetlands and rice paddies. In situ mapping indicated that soil-water interfaces act as hotspots, concentrating both organic pollutants and PPRIs by 9.30- and 4.27-folds, respectively. This synchronized colocation is the primary cause of the accelerated pollutant photolysis. Additionally, the contribution of each PPRI species to pollutant photolysis and a coupled transformation pathway at the soil-water interface significantly differed from those in bulk water. For instance, the contribution of singlet oxygen to metoxuron photolysis increased from 10.1% in bulk water to 44.4% at the soil-water interface. Our study highlights the rapid indirect photolysis of organic pollutants at the soil-water interfaces, offering new insights into the natural purification processes in wetlands as "Earth's kidneys."

C60 Fullerene-Induced Reduction of Metal Ions: Synthesis of C60-Metal Cluster Heterostructures with High Electrocatalytic Hydrogen-Evolution Performance.

Metal clusters, due to their small dimensions, contain a high proportion of surface atoms, thus possessing a significantly improved catalytic activity compared with their bulk counterparts and nanoparticles. Defective and modified carbon supports are effective in stabilizing metal clusters, however, the synthesis of isolated metal clusters still requires multiple steps and harsh conditions. Herein, we develop a C60 fullerene-driven spontaneous metal deposition process, where C60 serves as both a reductant and an anchor, to achieve uniform metal (Rh, Ir, Pt, Pd, Au and Ru) clusters without the need for any defects or functional groups on C60. Density functional theory calculations reveal that C60 possesses multiple strong metal adsorption sites, which favors stable and uniform deposition of metal atoms. In addition, owing to the electron-withdrawing properties of C60, the electronic structures of metal clusters are effectively regulated, not only optimizing the adsorption behavior of reaction intermediates but also accelerating the kinetics of hydrogen evolution reaction. The synthesized Ru/C60-300 exhibits remarkable performance for hydrogen evolution in an alkaline condition. This study demonstrates a facile and efficient method for synthesizing effective fullerene-supported metal cluster catalysts without any pretreatment and additional reducing agent.

C60 Fullerene‐Induced Reduction of Metal Ions: Synthesis of C60‐Metal Cluster Heterostructures with High Electrocatalytic Hydrogen‐Evolution Performance

AbstractMetal clusters, due to their small dimensions, contain a high proportion of surface atoms, thus possessing a significantly improved catalytic activity compared with their bulk counterparts and nanoparticles. Defective and modified carbon supports are effective in stabilizing metal clusters, however, the synthesis of isolated metal clusters still requires multiple steps and harsh conditions. Herein, we develop a C60 fullerene‐driven spontaneous metal deposition process, where C60 serves as both a reductant and an anchor, to achieve uniform metal (Rh, Ir, Pt, Pd, Au and Ru) clusters without the need for any defects or functional groups on C60. Density functional theory calculations reveal that C60 possesses multiple strong metal adsorption sites, which favors stable and uniform deposition of metal atoms. In addition, owing to the electron‐withdrawing properties of C60, the electronic structures of metal clusters are effectively regulated, not only optimizing the adsorption behavior of reaction intermediates but also accelerating the kinetics of hydrogen evolution reaction. The synthesized Ru/C60‐300 exhibits remarkable performance for hydrogen evolution in an alkaline condition. This study demonstrates a facile and efficient method for synthesizing effective fullerene‐supported metal cluster catalysts without any pretreatment and additional reducing agent.

RadicalPy: A Tool for Spin Dynamics Simulations.

Radical pairs (electron-hole pairs, polaron pairs) are transient reaction intermediates that are found and exploited in all areas of science, from the hard realm of physics in the form of organic semiconductors, spintronics, quantum computing, and solar cells to the soft domain of chemistry and biology under the guise of chemical reactions in solution, biomimetic systems, and quantum biology. Quantitative analysis of radical pair phenomena has historically been successful by a few select groups. With this in mind, we present an intuitive open-source framework in the Python programming language that provides classical, semiclassical, and quantum simulation methodologies. A radical pair kinetic rate equation solver, Monte Carlo-based spin dephasing rate estimations, and molecule database functionalities are implemented. We introduce the kine-quantum method, a new approach that amalgamates classical rate equations, semiclassical, and quantum techniques. This method resolves the prohibitively large memory requirement issues of quantum approaches while achieving higher accuracy, and it also offers wavelength-resolved simulations, producing time- and wavelength-resolved magnetic field effect simulations. Model examples illustrate the versatility and ease of use of the software, including the new approach applied to the magnetosensitive absorption and fluorescence of flavin adenine dinucleotide photochemistry, spin-spin interaction estimation from molecular dynamics simulations on radical pairs inside reverse micelles, radical pair anisotropy inside proteins, and triplet exciton pairs in anthracene crystals. The intuitive interface also allows this software to be used as a teaching or learning aid for those interested in the field of spin chemistry. Furthermore, the software aims to be modular and extensible, with the aim to standardize how spin dynamics simulations are performed.

Upgrading of kraft lignin pyrolysis products: Managing sulfur impurities

Pyrolysis stands as a powerful method for the valorization of biomass like kraft lignin, an aromatic-rich and sulfur-containing polymeric by-product from the pulping industry. Sulfur in the raw matrix is released during thermal processes and is redistributed in pyrolysis products. However, the presence of sulfur lowers the quality of products due to its corrosive and toxic character. In this work, commercial activated carbons have been used as adsorbents to remove the main sulfur compounds from the gas phase (i.e., CH3SH, COS, H2S). The analysis of sulfur content in biochar has been performed through SEM-EDXS, while the sulfur content in oils has been obtained by GC–MS analysis. The adsorption of sulfur on the activated carbon bed results in an enhancement of the release of sulfur in the gas phase from 34 % without activated carbon to 44 %. Up to 88 % of H2S removal is achieved after the adsorption step, together with a reduction of the overall sulfur content in the bio-oil rich in intermediates such as guaiacols and alkylated phenols. The residual sulfur contained in the liquid product is lowered to 3 % of the total sulfur in the system, thus improving the quality of the liquid pyrolysis product. This process limits the amount of sulfur in the gas and improves its quality and market value. At the same time, this results in a redistribution of sulfur in pyrolysis products such as bio-oil, improving its range of application as a source of chemical intermediates from kraft lignin.

Green Pathway of Urea Synthesis Through Plasma–Ice Interaction: Optimization and Mechanistic Insights With N2 + CO2 and NH3 + CO2 Gas Mixtures

ABSTRACTThis study presents a green approach for urea synthesis using plasma–ice interaction with N₂ + CO₂ and NH₃ + CO₂ gas mixtures. Plasma characterization via electrical and optical emission spectroscopy revealed that urea formation involves complex reactions driven by high‐energy species, producing reactive nitrogen and carbon intermediates. Plasma‐treated ice exhibited increased pH, electrical conductivity (EC), and reduced oxidation–reduction potential (ORP). Optimization of parameters, especially treatment time, significantly influenced urea formation. The NH₃ + CO₂ plasma produced a higher urea concentration (7.7 mg L−1) compared to the N₂ + CO₂ plasma (0.55 mg L−1) due to ammonia's greater reactivity. This method offers a sustainable, energy‐efficient alternative to traditional urea synthesis processes.

Glucose oxidation on gold in alkaline solution: A DEMS and microkinetic modeling study

The mechanism and kinetics of the electrochemical oxidation of glucose on gold surfaces in 0.1 M NaOH solution are investigated by rotating disk electrode and differential electrochemical mass spectrometry coupled to microkinetic modeling. For this purpose, the glucose mass-transport parameters (solution viscosity and density, glucose diffusion coefficient) were determined in the relevant conditions. Koutecký–Levich analysis of rotating disk electrode current-potential curves revealed that the glucose oxidation reaction (GOR) follows a one-electron mechanism at 0.6 V vs RHE, while H2 production could be evidenced by DEMS in this potential range. This suggests that the glucose oxidation selectively produces gluconate at 0.6 V vs RHE through an electrochemical oxidative dehydrogenation (EOD) mechanism. A microkinetic model of the current-potential curves was developed, taking into account the hydrogen electrode reactions kinetics, the dissociative adsorption/desorption of glucose, and the glucose electrooxidation on gold surfaces. The dissociative adsorption of glucose was found to be the rate-determining step of the reaction. It is also revealed that the release of anodic H2 through the Tafel step is triggered by the consumption of the adsorbed reaction intermediates. The gluconate electrooxidation into further products has to be considered for potential above 0.7 V vs RHE.

CO2 Reduction by Transition‐Metal Complex Systems: Effect of Hydrogen Bonding on the Second Coordination Sphere

AbstractHomogeneous electrocatalysts typified by transition‐metal complex show transcendent potency in efficient energy catalysis through molecular design. For example, metal complexes with elaborate design performed wonderful activity and selectivity for electrocatalytic CO2 reduction. Primary coordination sphere of metal complexes plays a key role in regulating its intrinsic redox properties and catalytic activity. However, the overall reduction efficiency of CO2 is also bound up with the substrate activation process. Transition‐metal complexes are hoped to exhibit reasonable redox potential, reactive activity, and stability, while binding and activating CO2 molecules to achieve efficient CO2 reduction. Construction of second coordination sphere, especially hydrogen‐bonding network of transition‐metal complexes, is reported to be the “kill two birds with one stone” strategy to realize efficient CO2 reduction catalysis via systematic catalyst properties modulation and substrate activation. Herein, we present recent progress on the construction of hydrogen‐bonding network in the second coordination sphere of metal complexes by ligand modification or the introduction of exogenous organic ligand, and the resulted productive enhancement of the catalytic performance of metal complexes by the improvement of adsorption capacity and activation of CO2, proton transfer rate, and stability of reaction intermediates, and so forth.

Interfacial Electronic Structure Engineering of NiCo2Se4 and NiTe2 Nanorods for Enhanced Hydrogen Evolution Reaction.

Finding the best candidates with outstanding electrocatalytic capabilities for the hydrogen evolution reaction is essential for realizing large-scale hydrogen production through electrolysis. In this study, we synthesized NiCo2Se4 (NCS) and NiTe2 (NT) nanorod arrays using a hydrothermal method. The confirmation of catalyst formation was achieved through X-ray diffraction analysis, electron microscopy imaging, and X-ray photoelectron spectroscopy. Leveraging the plentiful heterointerfaces and synergistic effects arising from the incorporation of bimetallic components, the NCS/NT electrocatalyst demonstrates remarkable efficacy in catalyzing the hydrogen evolution reaction. It achieves a minimal overpotential of 163 mV to attain a current density of 50 mA cm-2, showcasing exceptional catalytic activity. Further exploration has revealed that the engineering of heterogeneous interfaces and the morphology of nanorods not only guarantee the exposure of numerous active sites and expedite electron-mass transfer but also trigger electron modulation. Such modulation serves to fine-tune the adsorptive and desorptive dynamics of reaction intermediates, culminating in an enhancement of the catalyst's inherent activity. This study illuminates the novel composite electrocatalyst with robust synergy, highlighting the pivotal role of their unique nanostructures in achieving high-efficiency hydrogen production via electrolysis.

Threefold Impact on Reaction Coordinate Mapping of Zirconium Based Tri‐Chalcogenide Pseudo‐Monolayers as Emerging Ultrathin Catalysts for Water Splitting

AbstractThe continuous quest of finding optimum catalysts for photo‐electrocatalytic (PEC) water splitting has been revolving around 2D ultrathin materials because of the fact of exploiting both the surface area. In this work, a threefold impact is envisaged route to enhance the activity both in terms of hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in the emerging Zirconium Tri‐sulfides (ZrS3) based pseudo‐monolayers. Due to the unique and distinct electronic properties of the tri‐chalcogenide systems as compared to the di‐chalcogenide counterpart of Zirconium, one could afford to explore the implications of not only single‐atom functionalization and vacancy defect, but also the external strain to expedite the bifunctional catalytic activity in this promising material. Rigorous electronic structure calculations have been performed for the mentioned threefold effect on not only the band‐edge alignment, but going beyond to it by further constructing the reaction coordinate mapping corresponding to HER and OER mechanism. The repercussion of external strain in addition to the single atom functionalization and vacancy defect on the adsorption free energies of the prime intermediates of HER and OER reaction has been further correlated with the work function variation in this pseudo‐monolayer system.

Role of Oxide-Derived Cu on the Initial Elementary Reaction Intermediate During Catalytic CO2 Reduction.

The catalytic role of oxide-derived Cu (OD-Cu) in promoting CO2 reduction (CO2R) to C2+ products has been appreciated for decades. However, the dynamic evolution of the surface oxidation states, together with their real correlation to the binding of reaction intermediates, remains unclear due to technical challenges. Here, we show the time-resolved spectroscopic signatures of key OD-Cu-CO2•- intermediates during catalytic CO2 reduction through one electron transfer from nanoseconds to seconds time scale. We generated the initial intermediate CO2•- radicals in the bulk solution and monitored the interfacial reaction kinetics with well-defined OD-Cu (Cu(0), Cu(I), and Cu(II)) nanoparticles. Combined with molecular simulations, transient absorption profiles analysis reveals that Cu(I) induced a faster CO2•- radical coupling reaction than Cu(0), whereas Cu(II) is only reduced to Cu(I) by the CO2•- radical. Furthermore, the newly developed multistep cumulative pulse methodology uncovered the transition in chemical states of mixed OD-Cu during radical coupling reactions. This pulse radiolysis study provides compelling evidence for the beneficial role of subsurface oxides in early time catalytic CO2 transformation.

Metal‐Free Generation of Acyl Fluorides via Activation of Cyclopropyl Esters using a Hypervalent Iodine(III) Species and Selectfluor

AbstractAn efficient method for the activation of non‐activated cyclopropyl esters is developed using a hypervalent iodine(III) species and Selectfluor for the generation of acyl fluoride intermediates. The reactive acyl fluoride intermediate is smoothly transformed into various functional groups such as amides, esters, thioesters, and ketones depending on the nucleophile used in the in‐situ transformation. Utilizing the oxidation process of an iodoarene by Selectfluor, the activation is improved from a stoichiometric to catalytic protocol. Furthermore, the activation is employed in the chemoselective activation of target cyclopropyl ester in the presence of other ester moieties.

6‐Hydroxy Picolinohydrazides Promoted Cu(I)‐Catalyzed Hydroxylation Reaction in Water: Machine‐Learning Accelerated Ligands Design and Reaction Optimization

AbstractHydroxylated (hetero)arenes are privileged motifs in natural products, materials, small‐molecule pharmaceuticals and serve as versatile intermediates in synthetic organic chemistry. Herein, we report an efficient Cu(I)/6‐hydroxy picolinohydrazide‐catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) in water. By establishing machine learning (ML) models, the design of ligands and optimization of reaction conditions were effectively accelerated. The N‐(1,3‐dimethyl‐9H‐ carbazol‐9‐yl)‐6‐hydroxypicolinamide (L32, 6‐HPA‐DMCA) demonstrated high efficiency for (hetero)aryl bromides, promoting hydroxylation reactions with a minimal catalyst loading of 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; for substrates containing sensitive functional groups, the catalyst loading needs to be increased to 3.0 mol % under near‐room temperature conditions. N‐(2,7‐Di‐tert‐butyl‐9H‐carbazol‐9‐yl)‐6‐hydroxypicolinamide (L42, 6‐HPA‐DTBCA) displayed superior reaction activity for chloride substrates, enabling hydroxylation reactions at 100 °C with 2–3 mol % catalyst loading. These represent the state of art for both lowest catalyst loading and temperature in the copper‐catalyzed hydroxylation reactions. Furthermore, this method features a sustainable and environmentally friendly solvent system, accommodates a wide range of substrates, and shows potential for developing robust and scalable synthesis processes for key pharmaceutical intermediates.

6-Hydroxy Picolinohydrazides Promoted Cu(I)-Catalyzed Hydroxylation Reaction in Water: Machine-Learning Accelerated Ligands Design and Reaction Optimization.

Hydroxylated (hetero)arenes are privileged motifs in natural products, materials, small-molecule pharmaceuticals and serve as versatile intermediates in synthetic organic chemistry. Herein, we report an efficient Cu(I)/6-hydroxy picolinohydrazide-catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) in water. By establishing machine learning (ML) models, the design of ligands and optimization of reaction conditions were effectively accelerated. The N-(1,3-dimethyl-9H- carbazol-9-yl)-6-hydroxypicolinamide (L32, 6-HPA-DMCA) demonstrated high efficiency for (hetero)aryl bromides, promoting hydroxylation reactions with a minimal catalyst loading of 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; for substrates containing sensitive functional groups, the catalyst loading needs to be increased to 3.0 mol % under near-room temperature conditions. N-(2,7-Di-tert-butyl-9H-carbazol-9-yl)-6-hydroxypicolinamide (L42, 6-HPA-DTBCA) displayed superior reaction activity for chloride substrates, enabling hydroxylation reactions at 100 °C with 2-3 mol % catalyst loading. These represent the state of art for both lowest catalyst loading and temperature in the copper-catalyzed hydroxylation reactions. Furthermore, this method features a sustainable and environmentally friendly solvent system, accommodates a wide range of substrates, and shows potential for developing robust and scalable synthesis processes for key pharmaceutical intermediates.

Design of Stable Chiral Aminosulfonium Ylides and Their Catalytic Asymmetric Synthesis.

The isolation and catalytic enantioselective synthesis of configurationally stable S-stereogenic sulfonium ylides have been significant challenges in the field of asymmetric synthesis. These reactive intermediates are crucial for a variety of synthetic transformations, yet their inherent tendency towards rapid inversion at the sulfur stereocenter has hindered their practical utilization. Conventional approaches have focused on strategies that incorporate a C=S bond-containing cyclic framework to help mitigate this stereochemical lability. In this work, we present an alternative tactic that leverages the stabilizing influence of an adjacent N-atom and cyclic sulfide moiety. Exploiting a copper catalyzed enantioselective intermolecular carbene transfer reaction, structurally diverse S-stereogenic aminosulfonium ylides have been achieved in excellent yields and enantioselectivities. Experimental results indicate that the careful selection of 2-diazo-1,3-diketone precursors is crucial for achieving optimal stereoinduction in this transformation. The resulting highly enantioenriched aminosulfonium ylides allow for further stereospecific elaborations to furnish aminosulfonium ylide oxides and sulfinamide. This work expands the boundaries of chiral sulfonium ylide chemistry, providing access to a broad range of previously elusive S-stereogenic aminosulfonium ylide scaffolds.

Design of Stable Chiral Aminosulfonium Ylides and Their Catalytic Asymmetric Synthesis

AbstractThe isolation and catalytic enantioselective synthesis of configurationally stable S‐stereogenic sulfonium ylides have been significant challenges in the field of asymmetric synthesis. These reactive intermediates are crucial for a variety of synthetic transformations, yet their inherent tendency towards rapid inversion at the sulfur stereocenter has hindered their practical utilization. Conventional approaches have focused on strategies that incorporate a C=S bond‐containing cyclic framework to help mitigate this stereochemical lability. In this work, we present an alternative tactic that leverages the stabilizing influence of an adjacent N‐atom and cyclic sulfide moiety. Exploiting a copper catalyzed enantioselective intermolecular carbene transfer reaction, structurally diverse S‐stereogenic aminosulfonium ylides have been achieved in excellent yields and enantioselectivities. Experimental results indicate that the careful selection of 2‐diazo‐1,3‐diketone precursors is crucial for achieving optimal stereoinduction in this transformation. The resulting highly enantioenriched aminosulfonium ylides allow for further stereospecific elaborations to furnish aminosulfonium ylide oxides and sulfinamide. This work expands the boundaries of chiral sulfonium ylide chemistry, providing access to a broad range of previously elusive S‐stereogenic aminosulfonium ylide scaffolds.