In situ ligand-modulated activation of inert Ce(III/IV) into ozonation catalyst for efficient water treatment.

As a classic strategy to maximize catalytic activity, modulation of the electronic structure of central metal using organic ligands encounters great challenge in radical reactions exemplified by advanced oxidation processes (AOPs) due to operando destruction of employed ligands. Herein, we provide a paradigm achieving in situ ligand-modulated activation of the originally inert Ce(III/IV) for catalytic ozonation as a representative AOP widely applied in full-scale water treatment. Among the small-molecule carboxylates typically produced from pollutant degradation during ozonation, we find oxalate (OA) is a potent ligand to activate Ce(III/IV), inducing 11.5- and 5.8-fold elevation in rate constants of O3 decomposition and atrazine degradation, respectively. The Ce(III)-OA complex is proved the catalytic active species to boost pollutant degradation, while the catalytic ozonation unusually involves both •OH-dependent and •OH-independent pathways with comparable contributions. Both experiment and density functional theory calculation results show the pronounced electron donating effect of OA as evidenced by the substantial decreases in the charge residing on Ce, the ionization potential, and the Ce(III/IV) electrode potential, affords the activation of the Ce center for efficient ozonation. A comprehensive kinetic model involving 67 reactions is established to verify and elaborate the catalytic mechanism. Moreover, with in situ OA production, trace Ce3+ enables autocatalytic mineralization and codegradation of typical contaminants, which are not observed in case of Fe2+ or Cu2+. In addition, Ce3+ outperforms numerous state-of-the-art ozonation catalysts in terms of mass activity. This study sheds light on sustainable activation of the metal center harnessing operando ligands produced from the catalyzed reaction.

Visible Light-Mediated Late-Stage Thioetherification of Mercaptopurine Derivatives.

We disclose herein a novel and general radical approach to alkylthiopurines, encompassing 4 types of thiopurines, as well as their corresponding ribosides. This strategy is achieved through visible light-mediated late-stage functionalization of the sulfur atoms of mercaptopurines. The in situ-generated disulfide was proposed as the pivotal neutral intermediate for this transformation. We present herein a novel photo-mediated homolytic C-S bond formation for the preparation of alkylthiopurines and alkylthiopurine nucleosides. Despite the presence of reactive sites for the Minisci reaction, chemoselective S-alkylation remained the predominant pathway. This method allows for the late-stage introduction of a broad spectrum of alkyl groups onto the sulfur atom of unprotective mercaptopurine derivatives, encompassing 2-, 6-, and 8-mercaptopurine rings. Organoborons serve as efficient and eco-friendly alkylating reagents, providing advantages in terms of readily availability, stability, and reduced toxicity. Further derivatization of the thioetherified nucleosides, together with anti-tumor assays, led to the discovery of potent anti-tumor agents with an IC50 value reaching 6.1 µM (Comp. 31 for Jurkat).

A Practical and Modular Method for Direct C-H Functionalization of the BODIPY Core via Thianthrenium Salts.

Direct structural modification of small-molecule fluorophores represents a straightforward and appealing strategy for accessing new fluorescent dyes with desired functionalities. We report herein a general and efficient visible-light-mediated method for the direct C-H functionalization of BODIPY, an important fluorescent chromophore, using readily accessible and bench-stable aryl and alkenylthianthrenium salts. This practical approach operates at room temperature with extraordinary site-selectivity, providing a step-economical means to construct various valuable aryl- and alkenyl-substituted BODIPY dyes. Remarkably, this protocol encompasses a broad substrate scope and excellent functional-group tolerance, and allows for the modular synthesis of sophisticated symmetrical and asymmetrical disubstituted BODIPYs by simply employing different combinations of thianthrenium salts. Moreover, the late-stage BODIPY modification of complex drug molecules further highlights the potential of this novel methodology in the synthesis of fluorophore-drug conjugates.

An Efficient C-Si/C-H Cross-Coupling Reaction Enabled by a Radical Pathway.

The methods for the cross-coupling of aryl(trialkyl)silanes are long-standing challenges due to the extreme inertness of C-Si(R3) bond, though the reaction is environmentally friendly and highly regioselective to synthesize biaryls. Herein, we report a copper-catalyzed cross-coupling of aryl(trialkyl)silanes and aryl via a radical mechanism. The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, exhibits broad substrate scope, and provides an important synthetic strategy to acquire biaryls, exemplified by unsymmetrical fluorescence probes and late-stage functionalization of drugs. Of note, the experimental and theoretical mechanistic studies revealed a radical mechanism where the copper catalyst and CsF play critical roles on the radical generation and desilylation process.

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.

Harnessing in vivo synthesis of bioactive multiarylmethanes in Escherichia coli via oxygen-mediated free radical reaction induced by simple phenols.

BACKGROUND: Xanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluorescein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. RESULTS: In this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endogenous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial respiratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mutant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthrocolins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was responsible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biological active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also appeared in the rat blood. CONCLUSION: Our findings provide a mechanistic insight into in vivo synthesis of complex and condensed arthrocolins induced by simple phenols and exploits a quinol based method to generate endogenous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes.

Insights into mechanism of peroxymonosufate activation by Mo single-atom catalysts: Singlet oxygen evolution and role of Mo-N coordination.

Recently, the Fenton-like reaction using peroxymonosulfate (PMS) has been acknowledged as a potential method for breaking down organic pollutants. In this study, we successfully synthesized a highly efficient and stable single atom molybdenum (Mo) catalyst dispersed on nitrogen-doped carbon (Mo-NC-0.1). This catalyst was then utilized for the first time to activate PMS and degrade bisphenol A (BPA). The Mo-NC-0.1/PMS system demonstrated the ability to completely degrade BPA within just 20 min. Scavenging tests and density functional theory (DFT) calculations have demonstrated that the primary reactive oxygen species was singlet oxygen (1O2) produced by Mo-N4 sites. The self-cycling of Mo facilitated PMS activation and the transition from a free radical activation pathway to a non-radical pathway mediated by 1O2. Simultaneously, the nearby pyridinic N served as adsorption sites to immobilize BPA and PMS molecules. The exceptionally high catalytic activity of Mo-NC-0.1 derived from its unique Mo-N coordination, which markedly reduced the distance for 1O2 to migrate to the BPA molecules. The Mo-NC-0.1/PMS system effectively reduced the acute toxicity of BPA and exhibited excellent cycling stability with minimal leaching. This study presented a new catalyst with high selectivity for 1O2 generation and provided valuable insights for the application of single atom catalysts in PMS-based AOPs.

Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones.

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

Theoretical insights of the pharmaceutical compound fluoxetine in water: Role in direct photolysis and indirect photolysis by free radicals.

The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness, which may pose a major threat to the aquatic environment. In this study, photodegradation (direct and indirect photolysis) of two different dissociation states of fluoxetine (FLU) was investigated in water, mainly including the determination of photolytic transition states and products, and the mechanisms of indirect photodegradation with ·OH, CO3*- and NO3*. The main direct photolysis pathways are defluorination and C-C bond cleavage. In addition, the indirect photodegradation of FLU in water is mainly through the reactions with ·OH and NO3*, and the photodegradation reaction with CO3*- is relatively difficult to occur in the water environment. Our results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.

Degradation of organic pollutants accompanied by the ultrasonic separation of the spent lithium-ion battery cathode materials.

Since the majority of valuable components in spent lithium-ion batteries, such as lithium, exists in the electrode materials, common studies focused on the treatment of the cathode materials, which ignored the harm of residual electrolyte. The cavitation and thermal effects produced by ultrasonic can not only be used for the separation of electrode materials, but also have a wide range of applications in the field of sewage pollutant degradation. This work used ultrasonic to treat simulated electrolyte (propylene carbonate (PC)) solution of spent lithium-ion batteries, explored the effect of ultrasonic power, the addition amount of H2O2 solution (30 wt%) and reaction temperature on the degradation of electrolyte, and analysed the ultrasonic degradation reaction from the perspective of reaction kinetics. And the synchronous experiment of cathode material separation and electrolyte degradation was conducted under the optimal conditions. The results showed that the highest degradation efficiency of PC in the electrolyte was 83.08% under the condition of ultrasonic power of 900 W, the addition of H2O2 solution (30 wt%) of 10.2 mL, reaction temperature of 120°C and reaction time of 120 minutes, and the separation efficiency was 100%. This work reduced the environmental and health risks in the cathode material separation process and was conducive to the green development of spent lithium-ion battery recycling technology.

Electrochemically-Driven 1,4-Aryl Migration via Radical Fluoromethylation of N-Allylbenzamides: a Straightforward Access to Functionalized ß-Arylethylamines.

An electrochemical radical Truce Smiles rearrangement of N-allylbenzamides is documented herein. The selective 1,4-aryl migration was triggered by the radical fluoromethylation of the alkene providing a direct route to fluoro derivatives of the highly privileged ß-arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current to drive the oxidative process under mild reaction conditions. It accommodates a variety of migratory aryl groups with different electronic properties and substitution patterns. Careful selection of the protecting group on the nitrogen atom of the N-allylbenzamide is crucial to outcompete the undesired 6-endo cyclization and achieve high level of selectivity towards the 1,4-aryl migration. DFT calculations support the reaction mechanism and unveil the origin of selectivity between the two competitive pathways.

Catalytic Promiscuity of Fatty Acid Photodecarboxylase Enables Stereoselective Synthesis of Chiral α-Tetralones.

In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the  stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99%) and e.r. values (up to 99:1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FADox) / semiquinone state (FADsq) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of CvFAP promiscuity, and thus expands the reactivity repertoire of CvFAP and highlights the versatility of CvFAP in asymmetric synthesis.

Iron-Catalyzed Asymmetric α-Alkylation of 2-Acylimidazoles via Dehydrogenative Radical Cross-Coupling with Alkanes.

The direct α-alkylation of acyclic carbonyls with nonactivated hydrocarbons through C(sp3 )-H functionalization is both extremely promising and notably challenging, especially when attempting to achieve enantioselectivity using iron-based catalysts. We have identified a robust chiral iron complex for the oxidative cross-coupling of 2-acylimidazoles with benzylic and allylic hydrocarbons, as well as nonactivated alkanes. The readily available and tunable N,N'-dioxide catalysts of iron in connection with oxidants exhibit precise asymmetric induction (up to 99 % ee) with good compatibility in moderate to good yields (up to 88 % yield). This protocol provides an elegant and straightforward access to optically active acyclic carbonyl derivatives starting from simple alkanes without prefunctionalization. Density functional theory (DFT) calculations and control experiments were made to gain insight into the nature of C-C bond formation and the origin of enantioselectivity. We propose a radical-radical cross-coupling process enabled by the immediate interconversion between chiral ferric species and ferrous species.

Copper-Catalyzed Enantioselective C(sp3 )-SCF3 Coupling of Carbon-Centered Benzyl Radicals with (Me4 N)SCF3.

In contrast with the well-established C(sp2 )-SCF3 cross-coupling to forge the Ar-SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3 )-SCF3 bond has remained largely unexplored. We herein disclose a copper-catalyzed enantioselective radical C(sp3 )-SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4 N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino-oxazoline-derived anionic N,N,P-ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3 )-SCF3 cross-coupling of racemic benzyl halides and three-component 1,2-carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3 -containing molecules of interest in organic synthesis and medicinal chemistry.

Copper-Catalyzed Radical Allene C(sp2 )-H Cyanation.

While the hydrogen atom abstraction (HAA) from C(sp3 )-H bond has been well explored, the radical-mediated chemo- and regio-selective functionalization of allenic C(sp2 )-H bond via direct HAA from C(sp2 )-H bond of allene remains an unsolved challenge in synthetic chemistry. This is primarily due to inherent challenges with addition of radical intermediates to allenes, regioselectivity of HAA process, instability of allenyl radical toward propargyl radical et al. Herein, we report a copper catalyzed allenic C(sp2 )-H cyanation of an array of tri- and di-substituted allenes with exceptional site-selectivity, while mono-substituted allene was successfully cyanated, albeit with a low yield. In the developed strategy, steric N-fluoro-N-alkylsulfonamide, serving as precursor of hydrogen atom abstractor, plays a crucial role in achieving the desired regioselectivity and avoiding addition of N-centered radical to allene.

Metalloradical Catalysis: General Approach for Controlling Reactivity and Selectivity of Homolytic Radical Reactions.

Since Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic synthesis over the past two centuries has predominantly relied on the exploration and utilization of chemical reactions rooted in two-electron heterolytic ionic chemistry. While one-electron homolytic radical chemistry is both rich in fundamental reactivities and attractive with practical advantages, the synthetic application of radical reactions has been long hampered by the formidable challenges associated with the control over reactivity and selectivity of high-energy radical intermediates. To fully harness the untapped potential of radical chemistry for organic synthesis, there is a pressing need to formulate radically different concepts and broadly applicable strategies to address these outstanding issues. In pursuit of this objective, researchers have been actively developing metalloradical catalysis (MRC) as a comprehensive framework to guide the design of general approaches for controlling over reactivity and stereoselectivity of homolytic radical reactions. Essentially, MRC exploits the metal-centered radicals present in open-shell metal complexes as one-electron catalysts for homolytic activation of substrates to generate metal-entangled organic radicals as the key intermediates to govern the reaction pathway and stereochemical course of subsequent catalytic radical processes. Different from the conventional two-electron catalysis by transition metal complexes, MRC operates through one-electron chemistry utilizing stepwise radical mechanisms.

Visible-Light-Induced Three-Component Tetrafluoroethyl-heteroarylation of Alkenes with 1,1,2,2-Tetrafluoroethanesulfonyl Chloride and Quinoxalin-2(1H)-ones.

1,1,2,2-Tetrafluoroethyl-containing compounds are valuable structures due to their unique physicochemical properties, which have increasing potential application in drug discovery. However, synthetic methods for preparing such compounds are rare. Herein, we report the first use of 1,1,2,2-tetrafluoroethanesulfonyl chloride to introduce the HCF2 CF2 group into organic molecules via a three-component, radical tetrafluoroethyl-heteroarylation of alkenes with readily available quinoxalin-2(1H)-ones. This method provides a new and facile approach for late-stage functionalization of potential biologically active molecules.

Tracking SF5 I in the Iodopentafluorosulfanylation of Alkynes.

In the vibrant field of SF5 chemistry, SF5 X reagents (X=F, Cl, Br) are at the heart of current investigations in radical pentafluorosulfanylation reactions. SF5 I is the missing link whose existence has not been reported despite its potential as SF5 donor. This study reports the formal addition of the hitherto unknown SF5 I reagent to alkynes by means of a combination of SF5 Cl/KI/18-crown-6 ether. The exclusive regio- and stereoselective synthesis of unprecedented (E)-1-iodo-2-(pentafluoro-λ6 -sulfanyl) alkenes was achieved. A consensus was reached through computational and mechanistic studies for the realistic formation of SF5 - anion but not SF5 I in solution and the rational involvement of SF5 ⋅ and iodine radicals in the iodo pentafluorosulfanylation reaction.

Electrophotochemical Metal-Catalyzed Enantioselective Decarboxylative Cyanation.

In contrast to the rapid growth of electrophotocatalysis in recent years, enantioselective catalytic reactions powered by this unique methodology remain rare. In this work, we report an electrophotochemical metal-catalyzed protocol for direct asymmetric decarboxylative cyanation of aliphatic carboxylic acids. The synergistic merging of electrophotochemical cerium catalysis and asymmetric electrochemical copper catalysis permits mild reaction conditions for the formation and utilization of the key carbon centered radicals by combining the power of light and electrical energy. Electrophotochemical cerium catalysis enables radical decarboxylation to produce alkyl radicals, which could be effectively intercepted by asymmetric electrochemical copper catalysis for the construction of C-CN bonds in a highly stereoselective fashion. This environmentally benign method smoothly converts a diverse array of arylacetic acids into the corresponding alkyl nitriles in good yields and enantioselectivities without using chemical oxidants or pre-functionalization of the acid substrates and can be readily scaled up.

Pro-aromaticity Enabled Dealkenylative Functionalizations via Photo-Excitation and Oxidation.

A general and practical approach for diverse dealkenylative functionalization of olefin-containing substrates has been developed through the one-pot formation and utilization of pro-aromatic 1,4-dihydropyridazines using tetrazine as the key cycloaddition reagent. Triggered by either excitation or oxidation, the targeted C-C bonds in the 1,4-dihydropyridazine intermediates could be readily cleaved to generate alkyl radicals for subsequent transformations. Diverse carbon-carbon and carbon-hetero bond forming protocols, including Giese-type addition, hydrazination, borylation, Minisci-type alkylation, copper-catalyzed NH alkylation, acylation, alkynylation, cyanation, and azidation, are achieved in a highly modular fashion.