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Alcohols are common alkylating agents and starting materials alternative to harmful alkyl halides. In this study, a simple, benign and efficient pathway was developed to synthesize 1,3‐diphenylpropan‐1‐ols via the β‐alkylation of 1‐phenylethanol with benzyl alcohols. Unlike conventional borrowing hydrogen processes in which alcohols were activated by transition‐metal catalyzed dehydrogenation, in this work, t‐BuONa was suggested to be a dual‐role reagent, namely, both base and radical initiator, for the radical coupling of aromatic alcohols. The cross‐coupling reaction readily proceeded under transition metal‐free conditions and an inert atmosphere, affording 1,3‐diphenylpropan‐1‐ol with an excellent yield. A good functional group tolerance in benzyl alcohols was observed, leading to the production of various phenyl‐substituted propan‐1‐ol derivatives in moderate‐to‐good yields. The mechanistic studies proposed that the reaction could involve the formation of reactive radical anions by base‐mediated deprotonation and single electron transfer. [ABSTRACT FROM AUTHOR]

π-Coordination of an aryl chloride to a chromium carbonyl fragment promotes radical coupling with an arene in the presence of potassium tert -butoxide as a base and a catalytic amount of a spirobipyridine derivative as a promoter. After the removal of chromium under oxidative conditions, biaryl compounds are obtained in moderate to good yields. The chloroarene itself can be used as the substrate after arene exchange with a chromium naphthalene complex to generate the chromium chloroarene complex in situ, followed by radical reaction with an arene. [ABSTRACT FROM AUTHOR]

Aminoarenes are important molecules for broad applications in nearly all modern industries that involve chemicals. Direct and site‐selective C−H bond amination of arenes provides the most efficient and convenient method to prepare aminoarenes. A main challenge is to selectively install the amino group (or other functional groups) to the distal para‐carbon of arenes (especially multi‐substituted arenes) during the C−H bond functionalization events. Herein, we address this problem by designing a new strategy via a sequential radical dearomatization/radical amination/rearomatization process for para‐selective amination of benzyl alcohols. The para‐selectivity of our reaction is completely independent of the electronic and steric properties of the other substituents of the arene substrates. Aminoarenes with many substituents (up to full substitution) and diverse substitution patterns, including those difficult to synthesize previously, could be readily prepared using our protocols. Further exploration of the current strategy shall lead to other challenging C−H functionalization of arenes. [ABSTRACT FROM AUTHOR]

Abstract Efficiently assembling amino acids and peptides with bioactive molecules facilitates the modular and streamlined synthesis of a diverse library of peptide‐related compounds. Particularly notable is their application in pharmaceutical development, leveraging site‐selective late‐stage functionalization. Here, a visible light‐induced three‐component reaction involving arylthianthrenium salts, amino acid/peptide derivatives, and alkenes are introduced. This approach utilizes captodatively‐stabilized carbon radicals to enable radical‐radical C─C coupling, effectively constructing complex bioactive molecules. This method offers a promising alternative route for modular synthesis of peptide‐derived bio‐relevant compounds

Herein, we report the first electricity‐driven and metal‐free C(3)−H fluoroalkoxylation of quinoxalin‐2(1H)‐ones with both α‐monosubstituted and α,α‐disubstituted fluoroalkyl alcohols. This strategy features the advantages of convenience, mildness, effEctiveness and broad substrate practicality for synthesizing a new type of 3‐fluoroalkoxylated quinoxalin‐2(1H)‐ones. [ABSTRACT FROM AUTHOR]

β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis and medicinal chemistry. However, the introduction of a sterically demanding sidechain to the β‐carbon, such as an all‐carbon quaternary center, remains a significant challenge in classical polar processes. Recently, N‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged as a promising strategy to assemble highly crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity in these reactions remains highly challenging. In this work, we report our recent progress in controlling enantioselectivity for relay coupling of perfluoroalkyl and persistent vinylogous ketyl radicals. We developed a chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity in a critical bond‐forming event involving the coupling of a congested tertiary carbon radical and vinylogous ketyl radical. Chiral carboxylates bearing an all‐carbon quaternary center at the β‐position can be prepared in good yield and excellent enantiomeric excess. Results from density functional theory (DFT) calculations and nuclear Overhauser effect (NOE) experiments indicate that the N,N'‐diaryl squaramide motif adopts an unusual syn‐syn conformation, enabling hydrogen bonding interactions with the enolate oxygen, thereby rigidifying the overall conformation of the transition state. [ABSTRACT FROM AUTHOR]

The effects of the ferrocenyl moiety to enhance the nucleophilicity of the carbonyl group, situated at its adjacent position, have been explored in a series of α-ferrocenyl ketocarboxylic acids. In the presence of trifluoroacetic anhydride, 3-ferrocenoylpropionic acid and 4-ferrocenoylbutyric acid gave 5-ferrocenyl-4-trifluoroacetyl-2(3H)-furanone and 6-ferrocenyl-5-trifluoroacetyl-3,4-dihydropyran-2-one, respectively. Under similar reaction conditions, 2-ferrocenylcarbonylbenzoic acid, a keto carboxylic acid without a β-hydrogen, gave a dimerized lactone, 3,3′-diferrocenyl-3,3′-diphthalide, possibly due to radical coupling. The nucleophilic attack of carbonyl oxygen, activated by the ferrocenyl moiety, on the carboxylic carbon is assumed to be the crucial mechanistic step in forming these lactones. When the carbonyl group was reduced to an alcohol to break its conjugation with the ferrocenyl moiety, saturated lactones were isolated after the acidic workup. These results indicate that the α-ferrocenyl carbinols readily undergo solvolysis under acidic conditions, giving ferrocenylcarbenium ions, which are attacked by the carboxy oxygen to give lactones. [ABSTRACT FROM AUTHOR]

Photocatalytic oxidation, distinguished by its safety, controllability, mild conditions, and environmental friendliness compared to traditional oxidation reactions, has emerged as a prominent research focus in the forefront of chemistry, garnering widespread attention. However, its application in undergraduate teaching experiments has been limited by experimental conditions and equipment constraints. In this experiment, we devised a simple photoreaction device using conventional laboratory instruments. Employing a high-efficiency, low-energy sodium lamp as the light source to catalyze the oxidation of phosphate intermediates, we achieved the laboratory-scale synthesis of 1,2-dioxocycloethane-type medical chemiluminescence reagents, diversifying the application of photochemical reactions in experimental teaching. The materials and reagents used in this experiment are inexpensive and readily available, the operation is straightforward, and the yield of the product is high. The experiment allows for both independent single-bottle operations and the execution of multiple-bottle series reactions. Considering the experimental cost and teaching efficiency, we conducted group experimental teaching with a two-bottle series, fostering diverse teaching forms and nurturing students' cooperative skills. This approach is well-suited for undergraduate experimental teaching, aiding students in enhancing their comprehensive experimental operational abilities and deepening their understanding of reaction mechanisms such as radical coupling. [ABSTRACT FROM AUTHOR]

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine‐derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between α‐substituted enones and cyanoazaarenes or 2‐(chloromethyl)azaaren‐1‐iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone‐substituted tertiary carbon stereocenter at the β‐ or γ‐position of the azaarenes, are synthesized with high yields and ees. [ABSTRACT FROM AUTHOR]

The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2)−CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3)−CF3 bonds remains considerably restricted. In this work, we describe an efficient and site‐specific deaminative trifluoromethylation reaction of aliphatic primary amines to afford the corresponding alkyl trifluoromethyl compounds. The reaction proceeds at room temperature with readily accessible N‐anomeric amide (Levin's reagent) and bench‐stable bpyCu(CF3)3 (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Remarkably, the method can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules. Experimental mechanistic studies were conducted, and a radical mechanism is proposed, wherein the dual roles of Grushin's reagent have been elucidated. [ABSTRACT FROM AUTHOR]

A cascade one‐pot strategy to construct 31 examples of furo‐fused quinoxalines in up to 88% yields has been devised from readily accessible β‐ketothioamides and quinoxalin‐2‐ones in open flask at room temperature under TBHP mediated conditions. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of intermolecular radical coupling and intramolecular cyclization via desulfhydration of C=S bond cleavage. Generation of H2S as the only by‐product makes this process highly attractive. Furthermore, the photophysical behavior of the furo‐fused quinoxalines has also been studied. [ABSTRACT FROM AUTHOR]

A Cu/Pd co‐catalyzed Catellani‐type ortho arylation reaction of iodoarenes with aryl diazonium salts has been developed. Aryl radicals that derived from aryl diazonium salts were regioselectively installed at ortho position of iodoarenes via palladium catalyzed C−H activation. Mechanistic studies showed that, in contrast to classical Pd0−PdII−PdIV−PdII−Pd0 catalytic cycle, this radical cascades performed via a Pd0−PdII−PdIII−PdI−Pd0 cycle. [ABSTRACT FROM AUTHOR]

An expedient synthesis of silyl ethers is reported via photocatalytic free radical coupling of ketones with hydrosilanes and subsequent [1, 2]‐Brook rearrangement. This strategy features the advantages of 100 % atom economy, environmental friendliness, easily available starting materials as well as late‐stage functionalization of complex molecules. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of quinoxaline N-oxides through the radical-mediated cyclization of ketene N, S-acetals. The authors propose a new method using tert-butyl nitrite as a nitrogen source, which allows for the efficient synthesis of quinoxaline N-oxides in a regioselective manner. This research provides valuable insights into the synthesis of nitrogen-containing compounds and may have implications for drug development and other applications. Additionally, the document provides information on the synthesis and characterization of various quinoxaline derivatives, including their yields, physical properties, and spectroscopic data. This information can be useful for researchers studying quinoxaline derivatives and their potential applications. [Extracted from the article]

A visible light‐induced direct decarboxylative peroxidation of carboxylic acids under mild conditions has been disclosed. With this protocol, a variety of readily available carboxylic acids were converted to the peroxidation products in moderate to good yields via decarboxylative radical C−OO bond coupling. Tert‐butyl hydroperoxide acts as both the oxidant and peroxyl source, avoiding the use of transition metals or extra oxidants. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the photooxidation of the biomimetic model of C-terminal methionine, N-Acetyl-Methionine (N-Ac-Met), sensitized by a 3-Carboxybenzophenone (3CB) excited triplet in neutral and basic aqueous solutions. The short-lived transient species that formed in the reaction were identified and quantified by laser flash photolysis and the final stable products were analyzed using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS) and tandem mass spectrometry (MSMS). Based on these complementary methods, it was possible to calculate the quantum yields of both competing reactions, and the deprotonation was found to be favored over decarboxylation (for neutral pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.09, for basic pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.05). Findings on such a model system, which can possibly mimic the complex protein environment, are important in understanding complicated biological systems, for example, the studied compound, N-Ac-Met, can, to some extent, mimic the methionine in the C-terminal domain of β-amyloid, which is thought to be connected with the pathogenesis of Alzheimer’s disease.

A novel strategy for synthesizing structurally diverse 2‐pyrrolidinons by a NHC‐catalyzed tandem radical cyclization process has been developed. This reaction proceeds through a radical coupling approach, which not only shows broad substrate scope with excellent functional group compatibility but also is quite compatible with the secondary and tertiary radicals. By using this protocol, various potentially bioactive 2‐pyrrolidinons were facilely synthesized. [ABSTRACT FROM AUTHOR]

Considering the prevalence of alcohols and carboxylic acids, their fragment cross‐coupling reactions could hold significant implications in organic synthesis. Herein, we report a versatile method for synthesizing a diverse range of ketones from alcohols and carboxylic acid derivatives via N‐heterocyclic carbene (NHC) catalysis. Mechanistic investigations revealed that photoexcited xanthates and acyl azoliums undergo single electron transfer (SET) under photocatalyst‐free conditions, generating NHC‐derived ketyl radicals and alkyl radicals. These open‐shell intermediates subsequently undergo the radical‐radical cross‐coupling reaction, yielding valuable ketones. Furthermore, this approach can be employed in three‐component reactions involving alkenes and enynes, resulting in structurally diverse cross‐coupled ketones. The unified strategy offers a unique opportunity for the fragment coupling of a diverse range of alcohols and carboxylic acid derivatives, accommodating diverse functional groups even in complex settings. [ABSTRACT FROM AUTHOR]

In this work, we have systematically reviewed the till date disclosed routes pertaining to the synthesis of Parvaquone. Prior art search gave us around nineteen synthetic routes, involving invention and innovation towards the starting material selection and process path to synthesize Parvaquone. Interestingly, 2-hydroxy naphthalene-1,4-dione has been the predominant raw material used for the synthesis of Parvaquone. Every process was executed to attain higher atom economy, process economy, and better purity of the product. In most of the works, a significant focus was given on choosing cheap and easy-to-obtain raw materials/reagents. In the past six years, we have noticed the disclosure of mainly single and two-step processes with simple and mild reaction conditions for the preparation of Parvaquone. Only a few researchers had given an importance for the recovery and reuse of high-cost raw materials/reagents/solvents along with effluent management. If these aspects were collectively considered during the process development of drug, then the disclosed synthetic routes would become well accomplished for large-scale manufacturing. SYNOPSIS In this review work, we have gathered nineteen till date synthetic approaches of Parvaquone from the prior art disclosures. For the beneficial commercialization of Paravaquone, single or two-step processes would be favorable. This will provide much-needed control over the process of large-scale drug manufacturing. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the photooxidation of the biomimetic model of C-terminal methionine, N-Acetyl-Methionine (N-Ac-Met), sensitized by a 3-Carboxybenzophenone (3CB) excited triplet in neutral and basic aqueous solutions. The short-lived transient species that formed in the reaction were identified and quantified by laser flash photolysis and the final stable products were analyzed using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS) and tandem mass spectrometry (MSMS). Based on these complementary methods, it was possible to calculate the quantum yields of both competing reactions, and the deprotonation was found to be favored over decarboxylation (for neutral pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.09, for basic pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.05). Findings on such a model system, which can possibly mimic the complex protein environment, are important in understanding complicated biological systems, for example, the studied compound, N-Ac-Met, can, to some extent, mimic the methionine in the C-terminal domain of β-amyloid, which is thought to be connected with the pathogenesis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Classical aza-Reformatsky reaction generally involves excess reductants. Herein, we developed a visible light-induced catalytic asymmetric aza-Reformatsky reaction via a chiral Lewis acid-assisted direct excitation of imines without additional reductants, enabling the carbon-iodine bond cleavage of iododifluoromethyl ketones and the subsequent enantioselective radical coupling. This protocol provided an ingenious access to chiral β-amino ketones containing a gem-difluorine moiety. The mechanistic studies including radical trapping experiment, NMR experiment, electron paramagnetic resonance experiment, cyclic voltammetry experiment and spectroscopic analysis rationalized the reaction process., (© 2025 Wiley-VCH GmbH.)

Unnatural amino acids are important scaffolds for novel drug candidates, and especially α‐alkyl amino acids have emerged as a valuable variant. This is due to the ubiquity of alkyl groups, which are pervasive as key motifs in natural products, biological and pharmaceutical molecules. The development of radical‐based approaches in organic synthesis has expanded dramatically in recent years. It has enabled site‐ and region‐specific installation of a variety of functionalities in small molecules, which has been spontaneously applied in the preparation of versatile amino acid building blocks. The glycine motif in the backbone of amino acids has gained significant attention for allowing access to a variety of complex α‐unnatural amino acids via radical‐mediated α‐C−H alkylation. This review summarizes the last decade's development of radical‐based α‐C−H alkylation of glycine derivatives to provide unnatural α‐amino acids. The advantages, current limitations, and perspectives of glycine‐based unnatural amino acid synthesis are also discussed. [ABSTRACT FROM AUTHOR]

A manganese‐catalyzed regioselective ring‐opening peroxidation of cyclobutanols has been disclosed. With this protocol, the C(sp3)−OOBu‐t bond could be efficiently constructed via the radical‐mediated C−C bond cleavage/coupling, allowing the facile access to a variety of 4‐oxo peroxides. Besides, the obtained peroxidation products could be readily transformed into other synthetically attractive skeletons. [ABSTRACT FROM AUTHOR]

Catalysis by excited‐state palladium has emerged as an active area of research, but controlling the enantioselectivity remains a challenge. Herein, we report the use of synergistic Pd/Cu catalysis to accomplish the first three‐component photochemical 1,4‐bisalkylation reactions of 1,3‐butadiene. Consequently, α‐amino acid esters bearing quaternary stereocenters were expeditiously synthesized from three simple starting materials: an alkyl bromide, butadiene, and an aldimine ester. Experimental and computational investigation of the reaction mechanism confirmed a radical pathway involving catalysis by an excited‐state palladium species. The stereochemistry is mainly controlled by the chiral Cu catalyst. [ABSTRACT FROM AUTHOR]

Phytophenol dimerization, which is a radical-mediated coupling reaction, plays a critical role in many fields, including lignin biosynthesis. To understand the reaction, 2,2-diphenyl-1-picrylhydrazyl radical was used to initiate a series of phytophenol dimerization reactions in methanol. The products were identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) analysis in situ. The identified products mainly included biphenols, magnolol, honokiol, gingerol 6,6′-dimers, 3,6-dimethoxylcatechol β,β′ dimer, euphorbetin, bis-eugenol, dehydrodiisoeugenol, trans-ε-viniferin, (+) pinoresinol, and (−) pinoresinol. Structure–function relationship analysis allowed four basic rules to be defined: meta-excluded, C–C bonding domination, ortho-diOH co-activation, and exocyclic C=C involvement. The exocyclic C=C involvement, however, required conjugation with the phenolic core and the para-site of the -OH group, to yield a furan-fused dimer with two chiral centers. Computational chemistry indicated that the entire process was completed via a radical coupling reaction and an intramolecular conjugate addition reaction. Similar results were also found for the horseradish peroxidase (HRP)-catalyzed coniferyl alcohol dimerization, which produced (+) and (−) pinoresinols (but no (−) epipinoresinol), suggesting that the HRP-catalyzed process was essentially an exocyclic C=C-involved phytophenol dimerization reaction. The reaction was highly diastereoselective. This was attributed to the intramolecular reaction, which prohibited Re-attack. The four basic rules and diastereoselectivity can explain and even predict the main products in various chemical and biological events, especially oxidase-catalyzed lignin cyclization. [ABSTRACT FROM AUTHOR]

Herein a radical hydroxyalkylation of N‐heteroaromatics with aldehydes is reported. The constructive merging of photochemistry and electrochemistry is the key for the success of this atom‐economical Minisci method. This protocol highlights the utility of electrophotocatalysis to promote a practical and general synthesis of secondary alcohols in good yields from readily available N‐heteroaromatics and aldehydes under mild reaction condition. [ABSTRACT FROM AUTHOR]

Amidoboronates were prepared as a mixture of up to three isomers (rac5, meso5 and rac6) from the reductive coupling of N‐aryl iminoboronates with either cobaltocene or decamethylcobaltocene in acetonitrile. The interconversion of rac5 and rac6 isomers via rearrangement of their dynamic covalent B−N bonds was investigated in solution by redissolving isolated crystals. The aniline para substituent and catechol within the amidoboronates tuned the rac5/rac6 ratio; the rac6 isomer predominated for amidoboronates based on pyrocatechol, ranging from a ratio of 0 : 1 with electron‐withdrawing Cl substituents to 0.5 : 0.5 for electron‐donating NMe2 substituents. No interconversion was observed for the rac5 isomers of amidoboronates based on tetrachlorocatechol. Furthermore, the rac5/rac6 distribution was altered by catechol exchange of pyrocatechol for tetrachlorocatechol exploiting the dynamic covalent B−O bonds and the rac5 isomer was the major isomer following exchange. [ABSTRACT FROM AUTHOR]

Practical synthesis of polyolefin–polyvinyl block copolymers remains a challenge for transition‐metal catalyzed polymerizations. Common approaches functionalize polyolefins for post‐radical polymerization via insertion methods, yet sacrifice the livingness of the olefin polymerization. This work identifies an orthogonal radical/spin coupling technique which affords tandem living insertion and controlled radical polymerization. The broad tolerance of this coupling technique has been demonstrated for diverse radical/spin traps such as 2,2,5‐trimethyl‐4‐phenyl‐3‐azahexane‐3‐nitroxide (TIPNO), 1‐oxyl‐(2,2,6,6‐tetramethylpiperidine) ‐4‐yl‐α‐bromoisobutyrate (TEMPO‐Br), and N‐tert‐butyl‐α‐phenylnitrone (PBN). Subsequent controlled radical polymerization is demonstrated with nitroxide‐mediated polymerization (NMP) and atom transfer radical polymerization (ATRP), yielding polyolefin–polyvinyl di‐ and triblock copolymers (Đ<1.3) with acrylic, vinylic and styrenic segments. These findings highlight radical trapping as an approach to expand the scope of polyolefin‐functionalization techniques to access polyolefin macroinitiators. [ABSTRACT FROM AUTHOR]

Fluorine‐containing moieties are widely used in the pharmaceutical, agrochemical, and material fields. Thus, these structures are of immense interest in the fields of organic synthesis and medicinal chemistry. Among various fluorinated groups, the difluoromethyl unit has drawn increasing attention due to its unique pharmaceutical properties. In recent years, several methods for the synthesis of difluoromethylated compounds have been rapidly developed. However, most of these methods treat aromatic compounds with excess difluoromethylating reagents, which often contain organometallic compounds, so these transformations are generally less environmentally friendly and atom‐economical. In this review, we summarize the recent development of new methods for the synthesis of difluoromethyl motifs or difluoroalkenes from trifluoromethylated aromatic compounds or trifluoromethyl alkenes via single C(sp3)−F bond cleavage. [ABSTRACT FROM AUTHOR]

Examination of the reactions of σ‐type quinolinium‐based triradicals with cyclohexane in the gas phase demonstrated that the radical site that is the least strongly coupled to the other two radical sites reacts first, independent of the intrinsic reactivity of this radical site, in contrast to related biradicals that first react at the most electron‐deficient radical site. Abstraction of one or two H atoms and formation of an ion that formally corresponds to a combination of the ion and cyclohexane accompanied by elimination of a H atom ("addition‐H") were observed. In all cases except one, the most reactive radical site of the triradicals is intrinsically less reactive than the other two radical sites. The product complex of the first H atom abstraction either dissociates to give the H‐atom‐abstraction product and the cyclohexyl radical or the more reactive radical site in the produced biradical abstracts a H atom from the cyclohexyl radical. The monoradical product sometimes adds to cyclohexene followed by elimination of a H atom, generating the "addition‐H" products. Similar reaction efficiencies were measured for three of the triradicals as for relevant monoradicals. Surprisingly, the remaining three triradicals (all containing a meta‐pyridyne moiety) reacted substantially faster than the relevant monoradicals. This is likely due to the exothermic generation of a meta‐pyridyne analog that has enough energy to attain the dehydrocarbon atom separation common for H‐atom‐abstraction transition states of protonated meta‐pyridynes. [ABSTRACT FROM AUTHOR]

An efficient electrochemical dehydrogenative coupling reaction between amines and thiols at room temperature has been developed, which includes the formation of imine intermediate and N–S bond as key steps enabling rapid synthesis of N -sulfenylimines. The method successfully applies to a wide range of amines as well as structurally diverse thiols, exhibiting excellent functional group tolerance. The reaction also can be scaled up which provides an efficient and green method for N -sulfenylimines. An efficient cross dehydrogenative coupling reaction between amines and thiols under electrochemical conditions has been developed, which successfully applies to a wide range of amines as well as structurally diverse thiols providing N -sulfenylimines with up to 98 % yields. [Display omitted] • An interesting electrochemical coupling reaction between amines and thiols mediated by bromide ions was reported. • The reaction features mild conditions and wide substrate scope, also can be conducted in large-scale. • This reaction provides an efficient and green access to N -sulfenylimines. [ABSTRACT FROM AUTHOR]

Widespread occurrence of various heterocyclic aromatic compounds is reported in concentrations from 1 to 20 μg/L in surface and groundwater as well as influents and effluents of wastewater treatment plants around the world. These so-called emerging contaminants and their metabolites can cause adverse effects on the environment and humans, even at very low concentration, hence raised environmental concerns. In this study, feasibility of soybean peroxidase-catalyzed removal of three selected heterocyclic aromatics from water was investigated, including sensitivity to the most important operational conditions, pH (range 3.6–9.0), H2O2 concentration (range 0.10–1.50 mM), and enzyme activity (range 0.001–5.0 U/mL). 3-Hydroxycoumarin and 2-aminobenzoxaozle were found to be substrates for the enzyme, having ≥95% and 45% removal efficiency with most effective pHs of 7.0 and 6.0, respectively. Time course study was also conducted to determine the initial first-order rate constants and half-lives; half-lives normalized for enzyme activity (0.0257 and 452 min for the respective substrates) are compared with those of 21 other compounds reactive with soybean peroxidase. High-resolution mass spectrometry was employed to characterize the plausible oligomerization products of enzymatic treatment, which revealed formation of dimers and trimers of the two substrates. [ABSTRACT FROM AUTHOR]

Pinoresinol is a high-value monolignol-derived lignan used in plant defense and with human health-supporting effects. The synthetic yield and isolation efficiency of racemic pinoresinol from coniferyl alcohol by conventional radical coupling methods is sub-optimal. In this work, a facile and efficient synthetic approach was developed to synthesize pinoresinol with much higher yield. By using 5-bromoconiferyl alcohol, which was synthesized in high yield from 5-bromovanillin, to make 5,5′-bromopinoresinol via a peroxidase-mediated radical coupling reaction takes advantage of the smaller variety of radical coupling products from the 5-substituted monolignol, producing simpler product mixtures from which 5,5′-bromopinoresinol may be readily crystalized with good yield (total yield of 44.1% by NMR; isolated crystalline yield of 24.6%). Hydro-debromination of the crystalline 5,5′-bromopinoresinol to pinoresinol was essentially quantitative. Gram quantities of pinoresinol were conveniently synthesized by using this approach. This simple alternative pathway to make pinoresinol will impact pinoresinol-related research including structural characterization and modification of lignins, as well as clinical applications of pinoresinol and its derivatives.

The controlled release of well‐defined radical species under mild conditions for subsequent use in selective reactions is an important and challenging task in synthetic chemistry. We show here that simple bismuth amide species [Bi(NAr2)3] readily release aminyl radicals [NAr2]. at ambient temperature in solution. These reactions yield the corresponding hydrazines, Ar2N−NAr2, as a result of highly selective N−N coupling. The exploitation of facile homolytic Bi−Pn bond cleavage for Pn−Pn bond formation was extended to higher homologues of the pnictogens (Pn=N–As): homoleptic bismuth amides mediate the highly selective dehydrocoupling of HPnR2 to give R2Pn−PnR2. Analyses by NMR and EPR spectroscopy, single‐crystal X‐ray diffraction, and DFT calculations reveal low Bi−N homolytic bond‐dissociation energies, suggest radical coupling in the coordination sphere of bismuth, and reveal electronic and steric parameters as effective tools to control these reactions. [ABSTRACT FROM AUTHOR]

Herein, a conceptually distinct approach was developed that allowed for the dicarbofunctionalization of alkynes at room temperature using simple, bench‐stable alkyl iodides and a second molecule of alkyne as coupling partner. Specifically, the photochemical activation of palladium complexes enabled this strategic dicarbofunctionalization via addition of alkyl radicals from secondary and tertiary alkyl iodides and formation of an intermediate palladium vinyl complex that could undergo subsequent Sonogashira reaction with a second alkyne molecule. This alkylation–alkynylation sequence allowed the one‐step synthesis of 1,3‐enynes including heteroarenes and biologically active compounds with high efficiency without exogenous photosensitizers or oxidants and now opens up pathways towards cascade reactions via photochemical palladium catalysis. [ABSTRACT FROM AUTHOR]

A facile and general transition‐metal‐free access to 1‐substituted‐4‐quinazolinones 2 has been achieved based on the proline‐mediated cyclization of carbamoylbenzamides 1 in the presence of potassium t‐butoxides in DMSO at 100 °C within several hours. The gram‐scale synthesis of 1‐phenyl‐4‐quinazolinone 2 a has also been achieved without the loss of efficiency. The one‐pot synthesis of 1‐phenyl‐4‐quinazolinone 2 a has proven to be possible starting from 2‐bromobenzamide and phenylisocyanate in an acceptable yield. The present reactions were assumed to proceed through radical intermediates as the major path and also the SNAr route as a minor path based on several control experiments. [ABSTRACT FROM AUTHOR]

To facilitate C−C coupling in on‐surface synthesis on inert surfaces, we devised a radical deposition source (RDS) for the direct deposition of aryl radicals onto arbitrary substrates. Its core piece is a heated reactive drift tube through which halogenated precursors are deposited and en route converted into radicals. For the proof of concept we study 4,4′′‐diiodo‐p‐terphenyl (DITP) precursors on iodine‐passivated metal surfaces. Deposition with the RDS at room temperature results in highly regular structures comprised of mostly monomeric (terphenyl) or dimeric (sexiphenyl) biradicals. Mild heating activates progressive C−C coupling into more extended molecular wires. These structures are distinctly different from the self‐assemblies observed upon conventional deposition of intact DITP. Direct deposition of radicals renders substrate reactivity unnecessary, thereby paving the road for synthesis on application‐relevant inert surfaces. [ABSTRACT FROM AUTHOR]

The synthetic methodology for direct indole functionalizations is of great significance in indole chemistry and has been intensively investigated in the last few decades. From the perspective of green chemistry, oxygen is the best choice as the terminal oxidant in molecular synthesis. Hence, aerobic oxidative functionalization of indoles became a hot research topic in the last decade. Numerous efficient protocols in this field have been discovered that enable facile and efficient transformations of indoles to related valuable compounds, which are summarized and discussed in detail in this review. [ABSTRACT FROM AUTHOR]

The first palladium‐catalyzed direct benzylic C(sp3)−H chalcogenation with diaryl disulfides and diphenyl diselenide has been established. The coupling reaction proceeds between the thioether radical and palladiumcycle intermediate. Picolinamide serves as an excellent directing group for the C−H activation of benzylic C(sp3)−H and can be easily removed. The current protocol exhibits a relatively broad substrate scope and high functional group compatibility. A mechanistic study indicates that palladium(IV) intermediate is probably formed during the course of the reaction. [ABSTRACT FROM AUTHOR]

Radical reactions have been widely applied in C−P bond‐forming strategies. Most of these strategies require initiators, transition metal catalysts, or organometallic reagents. Herein, a transition metal‐free C(sp3)−P bond formation to prepare α‐aminophosphine oxides via deprotonative radical coupling processes of 2‐azaallyls with chlorodiphenylphosphine oxides was presented. Deprotonation of N‐benzyl imines may generate super‐electron‐donor (SED) 2‐azaallyl anions that reduced chlorodiphenylphosphine oxides to phosphine oxide radicals. Single‐electron transfer (SET) process transformed the 2‐azaallyl anions into 2‐azaallyl radicals, which may couple with phosphine oxide radicals to construct C−P bonds. The deprotonative radical coupling approach enables the synthesis of α‐aminophosphine oxides bearing various functional groups under mild conditions and without precious transition metal catalysts or oxidants. [ABSTRACT FROM AUTHOR]

A versatile strategy for the preparation of end‐functional polymers and block copolymers by radical exchange reactions is described. For this purpose, first polystyrene with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl end group (PS‐TEMPO) is prepared by nitroxide‐mediated radical polymerization (NMRP). In the subsequent step, these polymers are heated to 130 °C in the presence of independently prepared TEMPO derivatives bearing hydroxyl, azide and carboxylic acid functionalities, and polymers such as poly(ethylene glycol) (TEMPO‐PEG) and poly(ε‐caprolactone) (TEMPO‐PCL). Due to the simultaneous radical generation and reversible termination of the polymer radical, TEMPO moiety on polystyrene is replaced to form the corresponding end‐functional polymers and block copolymers. The intermediates and final polymers are characterized by 1H NMR, UV, IR, and GPC measurements. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2387–2395 [ABSTRACT FROM AUTHOR]

A pyridine–pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2pin2 as an electron‐transfer reagent. Complete regio‐ and cross‐selectivity are observed when forming a range of valuable 2,4′‐bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci‐type coupling involving a pyridyl radical. Instead, a radical–radical coupling process between a boryl phosphonium pyridyl radical and a boryl‐stabilized cyanopyridine radical explains the C−C bond‐forming step. [ABSTRACT FROM AUTHOR]

In this work, the first example of a radical stereodivergent reaction directed towards the stereoselective synthesis of both (R*,R*)‐ and (R*,S*)‐2,2′‐biflavanones promoted by samarium diiodide is reported. Control experiments showed that the selectivity of this reaction was exclusively controlled by the temperature. It was possible to generate a variety of 2,2′‐biflavanones bearing different substitution patterns at the aromatic ring in good‐to‐quantitative yields, being both stereoisomers of the desired compounds obtained with total or high control of selectivity. A mechanism that explains both the generation of the corresponding 2,2′‐biflavanones and the selectivity is also discussed. The structure and stereochemistry determination of each isomer was unequivocally elucidated by single‐crystal X‐ray diffraction experiments. [ABSTRACT FROM AUTHOR]

Isochromenes are important pharmacophores present in biologically active molecules and natural products. Their synthesis is generally limited to cyclization of phenyl propargyl ether precursors under transition metal catalyzed conditions. Herein, we present a novel disconnection that rapidly constructs isochromene derivatives through a cascade radical cyclization strategy. Generation of aryl radicals by SET reduction of 2‐iodo benzyl allenyl ethers is followed by radical cyclization to construct the isochromene core with formation of an allylic radical. The allylic radical then undergoes coupling with the azaallyl radical to give products in good to excellent yields. The elaborated 2‐iodo phenyl propargyl ether precursors can be used to construct isochromenes bearing various functional groups. [ABSTRACT FROM AUTHOR]