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Constructing highly proficient C–X (X = O, N, S, etc.) and C–C bonds by leveraging TMs (transition metals) (Fe, Cu, Pd, Rh, Au, etc.) and enzymes to catalyze carbene insertion into X–H/C(sp2)–H is a highly versatile strategy. This is primarily achieved through the in situ generation of metal carbenes from the interaction of TMs with diazo compounds. Over the last few decades, significant advancements have been made, encompassing a wide array of X–H bond insertions using various TMs. These reactions typically favor a stepwise ionic pathway where the nucleophilic attack on the metal carbene leads to the generation of a metal ylide species. This intermediate marks a critical juncture in the reaction cascade, presenting multiple avenues for proton transfer to yield the X–H inserted product. The mechanism of C(sp2)–H insertion reactions closely resembles those of X–H insertion reactions and thus have been included here. A major development in carbene insertion reactions has been the use of engineered enzymes as catalysts. Since the seminal report of a non-natural "carbene transferase" by Arnold in 2013, "P411", several heme-based enzymes have been reported in the literature to catalyze various abiological carbene insertion reactions into C(sp2)–H, N–H and S–H bonds. These enzymes possess an extraordinary ability to regulate the orientation and conformations of reactive intermediates, facilitating stereoselective carbene transfers. However, the absence of a suitable stereochemical model has impeded the development of asymmetric reactions employing a lone chiral catalyst, including enzymes. There is a pressing need to investigate alternative mechanisms and models to enhance our comprehension of stereoselectivity in these processes, which will be crucial for advancing the fields of asymmetric synthesis and biocatalysis. The current review aims to provide details on the mechanistic aspects of the asymmetric X–H and C(sp2)–H insertion reactions catalyzed by Fe, Cu, Pd, Rh, Au, and enzymes, focusing on the detailed mechanism and stereochemical model. The review is divided into sections focusing on a specific X–H/C(sp2)–H bond type catalyzed by different TMs and enzymes. [ABSTRACT FROM AUTHOR]

A simple and efficient three‐component coupling reaction of carboxylic acids, diazo compounds, and tertiary amines catalyzed by manganese has been described. This reaction proceeds smoothly under mild conditions to afford various β‐amino esters in moderate to good yields by using O2 as the terminal oxidant. In this process, Mn‐based carbene radical, single‐electron transfer, and nucleophilic attack were fused into a reaction system. [ABSTRACT FROM AUTHOR]

N‐Heterocyclic carbene (NHC)‐derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen‐containing compounds, it is surprising to note that the use of NHC‐derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC‐derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine‐bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one‐pot, multicomponent transesterification reaction between selenoureas, α‐diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines. [ABSTRACT FROM AUTHOR]

[3+2]‐Cycloaddition reactions of 3‐trifluoromethyl‐2H‐thiete 1,1‐dioxide, 4(5)‐trifluoromethyl‐2,3‐dihydrothiophene 1,1‐dioxides and 5(6)‐trifluoromethyl‐3,4‐dihydro‐2H‐thiopyrane 1,1‐dioxides with diazomethane proceed with the formation of regioisomeric mixtures of corresponding dihydropyrazole‐fused cycloadducts. Reactions of 3‐trifluoromethyl‐2H‐thiete 1,1‐dioxide with ethyl diazoacetate and in situ generated 2,2,2‐trifluorodiazoethane lead to the regioselective formation of pyrazolino‐sultine derivatives via rearrangement of initially formed pyrazoline‐fused thietane 1,1‐dioxides. Treatment of 3‐trifluoromethyl‐2H‐thiete 1,1‐dioxide and 4‐trifluoromethyl‐2,3‐dihydro‐thiophene 1,1‐dioxide with in situ generated N‐phenyl nitrilimines gives rise to dihydropyrazole‐ thietane 1,1‐dioxides and tetrahydrothiophene 1,1‐dioxides, respectively, in a regioselective fashion. [ABSTRACT FROM AUTHOR]

Metal carbene transfer reactions have been well-established as an indispensable tool in modern organic synthesis, especially in the construction of C–C and C–X bonds with high efficiency and selectivity. Among these, stepwise carbene transfer reaction with alkenes beyond classical cyclopropanation reaction has been demonstrated as a practical method for the effective olefinic C–H/C–C bond functionalization. This review highlights the recent achievements in this area for the direct C–C bond formation involving metal carbene species with alkenes through a through stepwise reaction pathway. The content of this review is organized into three general categories according to the types of the reactions, including (i) direct nucleophilic addition of alkenes with metal carbene species, (ii) cross-coupling reaction via an alkenylic C–H bond activation and migration insertion sequence, and (iii) catalytic coupling reaction involving radical intermediate. Considering this rapidly evolving field, detailed reaction mechanism, current limitations, and future research directions are discussed. 1 Introduction 2 Nucleophilic Addition of Alkenes to Metal Carbene Species 2.1 Using Polarized Alkenes 2.2 Using Unactivated Alkenes 2.3 Cascade Reactions 3 Cross-Coupling Reaction Involving Metal Carbene Migratory Insertion Process 4 Coupling Reaction Involving Radical Intermediate 5 Conclusions and Perspectives [ABSTRACT FROM AUTHOR]

Decomposition of aryl and unsubstituted diazo ester into Rh(II)‐carbenes by the [(IMes)Rh2(OAc)4] complex is shown to be slower than with Rh2(OAc)4. Diazo esters substituted by a second electron‐withdrawing group do not suffer nitrogen extrusion when exposed for several hours to this (NHC)Rh(II) complex at room temperature. This chemoselective decomposition of diazo esters depending on their substituent (Ar, H, EWG) can furthermore be achieved on a mixture of substrates. The catalytic activity of [(IMes)Rh2(OAc)4] towards electron‐poor diazo compounds is also restored by heating to reflux in chloroform, or after decomplexation of the NHC by addition of GaCl3. The [(IMes)Rh2(OAc)4] complex was then used to induce a fully selective reaction cascade from a mixture of two diazo esters. First, a donor/acceptor diazo compound was decomposed selectively at room temperature to give an intermolecular O−H insertion product without any decomposition of the electron poor diazo compound. Addition of GaGl3 then triggered nitrogen extrusion from the diazo malonate to give a 1,5‐C−H insertion product. This transformation, where decomposition of diazo compounds catalyzed by Rh(II) complexes can be externally controlled, represents the first example of assisted tandem catalysis with two metal carbene precursors. [ABSTRACT FROM AUTHOR]

The cleavage of carbophosphinocarbenes and carbodicarbenes with nitrous oxide (N2O) leads to the formation of room‐temperature stable diazoalkenes. The utility of Ph3P/N2 and NHC/N2 ligand exchange reactions were demonstrated by accessing novel benzimidazole‐ and benzothiazole derived diazoalkenes, which are not accessible by the current state‐of‐the‐art methods. The stable diazoalkenes subsequently allow further ligand exchange reactions at C(0) with carbon monoxide, isocyanide, or a diamidocarbene (DAC). Overall, the combination of hitherto unknown NHC/N2 and N2/L (L = DAC, CO, R−NC) ligand exchange reactions at a C(0) center allow the selective functionalization of the carbodicarbene ligand structure which represents a new methodology to rapidly assemble novel carbodicarbenes or cumulenic compounds. [ABSTRACT FROM AUTHOR]

A highly efficient catalytic nucleophilic addition of 3‐substituted oxindoles to 3‐diazo oxindoles has been achieved. This method relies on an organic base catalysis system, which can simultaneously activate 3‐substituted oxindoles as a nucleophile and the diazo compounds as a strong N‐terminal electrophile. Importantly, this approach could yield a broad array of functionalized isatin‐hydrazones featuring an adjacent tetrasubstituted carbon centre of the N(sp3) atom. [ABSTRACT FROM AUTHOR]

A wide range of α-aryl-α-diazophosphonates were easily prepared via modified diazo transfer reaction. Benzylphoshonates reacted with tosyl azide (TsN3) in the presence of potassium tert -butoxide (KO t Bu) to afford diazophosphonates in yields up to 93% (generally 70–80%). Aryldiazophosponates were successfully explored for the synthesis of 5-aryl-substituted pyrazol-3-carboxylates in one pot by the 1,3-dipolar cycloaddition with alkyl acrylates followed by NaH treatment. The second stage led to elimination of the diethoxylphosphoryl moiety with the aromatization of cycle. [ABSTRACT FROM AUTHOR]

The art of dyeing textiles has a long history, as natural dyes have been used since prehistoric times. With the development of synthetic dyes in the 19th century, the focus shifted from natural to synthetic dyes due to their superior properties. Recently, however, interest in natural dyes has increased again due to environmental and health concerns. Among industrial dyes, heterocyclic dyes, especially azo dyes, are of great importance due to their color brilliance and fastness. This review examines the synthesis, application, and analysis of azo dyes, especially heterocyclic dyes. It deals with monoazo, diazo, and polyazo dyes and highlights their structures, synthesis methods, and fastness properties. In addition, the ecological impact of azo dyes and practical solutions for their synthesis and application are discussed. [ABSTRACT FROM AUTHOR]

The present review covers various advances in the field of metal‐catalyzed coupling of N‐tosylhydrazones with compounds containing C−H/heteroatom‐H bonds, including transition metal catalysts i. e. Pd, Rh, Cu, Ag, Ni and Co and resulting alkylated, alkenylated, alkynylated, allenylated, annulated and many other products. A metal carbene migratory insertion process play a key role in carbon‐carbon single bond (C−C) and carbon‐carbon double bond (C=C) formation and undergoes variety of cascade reactions to synthesize a wide scope of pharmaceutically and medicinally valuable scaffoldings. [ABSTRACT FROM AUTHOR]

Diazo peptides have been described earlier, however, due to their high reactivity have not been broadly used until today. Here, we report the preparation, properties, and applications of chemically stable internal diazo peptides. Peptidyl phosphoranylidene‐esters and amides were found to react with triflyl azide primarily to novel 3,4‐disubstituted triazolyl‐peptides. Nonaflyl azide instead furnished diazo peptides, which are chemically stable from pH 1–14 as amides and from pH 1–8 as esters. Thus, diazo peptides prepared by solid phase peptide synthesis were stable to final deprotection with 95 % trifluoroacetic acid. Diazo peptides with the recognition sequence of caspase‐3 were identified as specific, covalent, and irreversible inhibitors of this enzyme at low nanomolar concentrations. A fluorescent diazo peptide entered living cells enabling microscopic imaging and quantification of apoptotic cells via flow cytometry. Thus, internal diazo peptides constitute a novel class of activity‐based probes and enzyme inhibitors useful in chemical biology and medicinal chemistry. [ABSTRACT FROM AUTHOR]

A metal-free system for Doyle–Kirmse reaction of biologically important diallyl sulfide with donor–acceptor diazo compounds in an aqueous medium using blue-LED irradiation was demonstrated. The resulting sulfanyl dienes were converted into thiopyrans using ring-closing metathesis in water. Additionally, the utility of dihydro-thiopyrans was also investigated. [ABSTRACT FROM AUTHOR]

An efficient strategy has been developed for the synthesis of 3‐substituted lawsones using a catalytic amount of Sc(OTf)3 in toluene at −78 °C through a Buchner‐Curtius‐Schlotterbeck reaction. It is a versatile method to produce a large number of 3‐aryl, 3‐styryl, 3‐alkyl, and 3‐heteroaryl substituted lawsones under mild conditions. This is a first report on the synthesis of 3‐substituted lawsones in high yields with in short reaction times. [ABSTRACT FROM AUTHOR]

Herein, a microwave promoted tandem reaction of free primary arylamines with diazo compounds in water for clean synthesis of 2,2‐disubstituted 3‐oxindoles is present. Water plays important roles in the whole cascade process: O−H insertion to diazo, air oxidation, ortho C−H functionalization, cyclization and 1,2‐ester migration. In particular, water plays a mediation role in the site selective ortho‐C−H addition. [ABSTRACT FROM AUTHOR]

A copper-catalyzed three-component reaction of diazo compounds, nitriles, and azodicarboxylates to construct 2,3-dihydro-1,2,4-triazoles is reported. Key to the success is the utilization of azodicarboxylates to trap the in-situ formed nitrile ylides from diazo compounds by [3 + 2]-cycloaddition. Both the acceptor-only and donor-acceptor diazo compounds are all tolerated to the strategy. The synthetic value of this protocol is illustrated by gram-scale synthesis and valuable transformation of the obtained 2,3-dihydro-1,2,4-triazoles. [ABSTRACT FROM AUTHOR]

Control of the regioselectivity of nucleophiles toward alkylating agents is a fundamental problem in heterocyclic chemistry. Substrate-controlled TfOH-catalyzed alkylation of 4-hydroxycoumarin with diazo compounds has been developed to provide rapid access to the C3- or O-alkylated 4-hydroxycoumarins with high efficiency. The regioselectivity can be determined by varying the electronic nature of the diazo substrates, especially those bearing a methylthio group. [ABSTRACT FROM AUTHOR]

Thanks to the ability of diazo derivatives to react either as 1,3‐dipoles and as carbenes after dinitrogen extrusion, combinations of oxa or aza benzonorbornadienes and diazomalonates afford polycyclic pyrazolidines via a three‐step sequence of (i) a highly diastereoselective [3+2]‐cycloaddition, (ii) a CpRu‐catalyzed carbene addition, and (iii) a second dipolar cycloaddition. Of importance, step (II) represents a unique access to novel bench‐stable N,N‐cyclic azomethine imines, which behave as effective 1,3‐dipoles in combination with electron‐poor dipolarophiles. Each step proceeds efficiently and the 3‐step process can be performed in one‐pot to yield a polycyclic pyrazolidine in excellent overall yield (90 %). [ABSTRACT FROM AUTHOR]

Diazo compounds and organic azides are widely used as reagents for accessing valuable molecules in multiple areas of fundamental and applied chemistry. Their capacity to undergo versatile chemical transformations arises from the reactive nature of an incipient dinitrogen molecule at the terminal position. In this work, we report the synthesis and characterization of an N-heterocyclic carbene (NHC)– stabilized diazoborane—a boron-centered analog of organic azides and diazoalkanes. The diazoborane displays a strong tendency to release dinitrogen, thus serving as a borylene source, in analogy to organic azides and diazoalkanes serving as nitrene and carbene sources, respectively. Also reminiscent of diazoalkane and organic azide reactivity, the diazoborane serves as a 1,3-dipole that undergoes uncatalyzed [3+2] cycloaddition with an unactivated terminal alkyne, affording a five-membered heterocycle after a two-step rearrangement. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed carbene transfer reactions have a century‐old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two‐electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem‐dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons–Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal 1,1‐dehydrogenation. These reactions are currently restricted to substrates containing electron‐withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion. [ABSTRACT FROM AUTHOR]

Fluorinated organic compounds represent an important and growing family of active ingredients in various fields, including material science, pharmaceutical chemistry and biological science. Developing efficient synthetic methods toward fluorinated organic compounds have attracted much attention. In recent years, transition‐metal catalyzed reaction of trifluoro diazo compounds were a powerful and convenient approach to afford trifluoromethyl‐ and difluoromethyl‐substituted compounds of value. In this review, the recent progress on transition‐metal‐catalyzed reactions involving trifluoro diazo compounds and their surrogates via trifluoromethylated transition‐metal carbene complex is described in the sequence of 2,2,2‐trifluorodiazoethane as carbene precursor, ethyl 3‐trifluoro‐2‐diazo‐propionate as carbene precursor, trifluoroethylamine hydrochloride or amines as the CF3CHN2 surrogate as well as trifluoro aldehydes/ketones N‐sulfonylhydrazones as the trifluoro diazo compounds surrogate. [ABSTRACT FROM AUTHOR]

A hitherto unknown class of C4‐symmetric Caryl−Cβ (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)−H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2‐hydroxymethyl‐3‐naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), the C4‐symmetric α,α,α,α‐atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C−H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir‐complex 3 e, the 2‐substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities. [ABSTRACT FROM AUTHOR]

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β‐carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β‐carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo‐/enantio‐selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β‐carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products. [ABSTRACT FROM AUTHOR]

Alkenes are highly valuable materials in organic synthesis, and their three‐component reactions offer a promising method for C−C bond formation and carbon chain elongation. This approach not only reduces the number of reaction steps but also minimizes waste generation, enabling the preparation of polysubstituted alkanes from simple starting materials. In this review, we provide an overview of recent advancements in this field from 2013 to 2023. We have classified the developments into three main categories: (1) reactions triggered by C‐radicals or heteroatom‐radicals; (2) cascades involving three‐membered ring intermediates; and (3) transformations catalyzed by metals. We will discuss a wide range of reactions that involve diazoium salts, arylhydrazines, acids, aldehydes, 1,3‐dicarbonyls, diazo compounds, amines, malononitriles, diacyl peroxides, ethers, 1,3‐dithiane, arenes, CuSCF3, selectfluor, Et3N ⋅ 3HF, TBHP, CH2Cl2, CHCl3, CO2, CO, KCl, H2O, and other reagents. These reactions lead to alkylation, arylation, or carbonylation products. We believe that this review will be helpful for future research in this area. [ABSTRACT FROM AUTHOR]

The three-component reaction of a diazo compound, azide and allylboronate was explored, and Rh2(esp)2 was utilized as the optimal catalyst. A series of α-amino esters were efficiently produced from the ethyl diazoacetate in 57–84% yields, and excellent diastereoselectivities were observed with the reaction employing (E)-allylboronate as the alkylation reagent. The α-amino ketone or homoallylic amine could also be prepared by using α-diazo ketone or trimethylsilyl diazomethane in acceptable yields. [ABSTRACT FROM AUTHOR]

We here reported a highly stereoselective method for the synthesis of polysubstituted conjugated dienes from α‐aryl α‐diazo alkynyl ketones and pyrazole‐substituted unsymmetric aminals under mild conditions, which was promoted by photo‐irridation and involved with 1,6‐dipolar intermediate and quadruple sigmatropic rearrangements, was successfully developed. In this transformation, the cleavage of four bonds and the recombination of five bonds were implemented in one operational step. This protocol provided a modular tool for constructing dienes from amines, pyrazoles and α‐alkynyl‐α‐diazoketones in one‐pot manner. The results of mechanistic investigation indicated that the plausible reaction path underwent the 1,6‐sigmatropic rearrangement instead of the 1,5‐sigmatropic rearrangement. [ABSTRACT FROM AUTHOR]

This article discusses the use of photocatalysis in [2,3]-sigmatropic rearrangement reactions of diazo compounds. Metal catalysts are commonly used to access the carbene fragment necessary for these reactions, but visible-light-mediated transformations have gained interest for their green and sustainable synthesis potential. The authors explore the use of heavy atoms and organosulfur compounds as catalysts in these reactions, and optimize the conditions using ruthenium catalysts. The photocatalytic rearrangement reactions are found to be efficient and yield moderate to high yields of the desired products. [Extracted from the article]

The chemoselective N-H insertion of unsymmetrical diamines into carbene is a longstanding challenge. A simple copper-catalyzed strategy for synthesizing C-substituted piperazinones is described, employing easily accessible diazo compounds and 1,2-diamines. The reaction proceeded via chemo-selective carbene insertion at the comparatively less nucleophilic amine, followed by instantaneous cyclization. The protocol was further extended to access NH-free piperazinone, and the synthesis of a Mianserin derivative. [ABSTRACT FROM AUTHOR]

Summary Peter Griess synthesized the first diazo compounds in 1858. August Kekulé played a key role in the elucidation of the structure of this new class of compounds. Around 1886, the photosensitivity of diazo compounds was discovered. This was used to develop the diazotype, a silver‐free copying process which produces azo dyes. Finally, a suggestion is made on how the diazotype can be implemented in chemistry classes. [ABSTRACT FROM AUTHOR]

A method for synthesizing silyl arylsulfonyl hydrazones as silyldiazomethane precursors has been developed. Although silyldiazomethanes are an important class of diazo compounds, their use in intramolecular cyclization reactions has not been fully explored despite the rich chemistry of diazo compounds, particularly metal carbenoid chemistry. The fundamental challenge underlying the absence of such studies is the lack of a method for synthesizing silyldiazomethanes with functional groups that can react with metal carbenoids. The method reported here provides access to variety of silyl arylsulfonyl hydrazones with functional groups such as ethers, carbamates, and alkynes, which can serve as reaction sites for metal carbenoids. A one‐pot hydrazone formation using unstable formylsilane formed in situ is key to a successful synthesis. The use of 2,4,6‐trimethylbenzenesulfonohydrazide contributed toward achieving broad generality in hydrazone formation. The synthetic potential of this method was demonstrated through the generation of silyldiazomethane and its transformation to several silacycles. [ABSTRACT FROM AUTHOR]

Diazo compounds are gathering interest for their potential in promoting greener synthesis routes. We investigate, at a lab‐scale, the continuous synthesis of diazo acetonitrile (DAN) using a micro‐structured flow reactor and a flow reaction calorimeter. Data concerning DAN formation in the former, and relative to reaction heat and gas flow rate in the latter, are collected. We present a physical and a grey‐box model, both of which are calibrated to our data. Compared to the physical model, the grey‐box approach allows to better incorporate the complex chemical reaction pathways of DAN. [ABSTRACT FROM AUTHOR]

Diazo compounds, although possessing unique reactivity, have been widely rejected due to their highly hazardous preparation protocols. Diazoacetonitrile (DAN), a relatively stable diazo compound, has been overlooked despite its potential in chemical synthesis. The present study describes a microflow process for the simultaneous preparation of DAN in aqueous solution and its extraction in dichloromethane. The DAN productivity was optimized in terms of solvent, temperature, residence time, and pressure. This experimental work represents a breakthrough in delivering DAN continuously in a stable CH2Cl2 solution, enabling its utilization as a versatile building block for various synthetic processes and contributing to the development of new green synthetic processes. [ABSTRACT FROM AUTHOR]

Corynebacterium pseudotuberculosis causes infection in goats, sheep, cattle, and humans. The disease imposing huge economic losses such as reducing milk, meat, and wool production and downgrading and condemnation of affected carcass to goat-rearing industry. Despite all its devastating effects, no effective antimicrobial was suggested for the treatment of this pathogen due to its highly resistant nature. Development and utilization of nanoparticles has paved the way to revive the efficacy of conventional antibiotics. Encapsulation of antibiotics within liposome as a nanoparticle may present a potential approach for successful treatment of resistant bacterial infections. The aim of this research was therefore to evaluate the antibacterial activity of free and liposome-encapsulating tylosin against Corynebacterium pseudotuberculosis. The minimum inhibitory concentration of free and liposome-encapsulated tylosin was determined by microbroth dilution and resazurin colorimetric-based methods. The antibiofilm activity of free and liposomal tylosin was assessed by crystal violet and resazurin techniques. Acridine orange/ethidium bromide staining assay was performed to assess the effect of free and liposomal tylosin on pre-formed biofilm of Corynebacterium pseudotuberculosis. The findings demonstrated minimum inhibitory concentration value of 1 µg/mL and 32 µg/mL for free and liposomal tylosin, respectively. The biofilm inhibitory data showed that free tylosin inhibited the formation of Corynebacterium pseudotuberculosis at 2 µg/mL, while this concentration was 64 µg/mL for liposomal tylosin. The antibiofilm concentration was 1024 µg/mL and 2048 µg/mL for liposome-encapsulated and free tylosin, respectively. It can be concluded that liposome as a nanocarrier can offer an excellent system of drug delivery for enhancing the efficacy of antibiotics against resistant form of Corynebacterium pseudotuberculosis. [ABSTRACT FROM AUTHOR]

While in nature, reactions occur in water-based confined compartments, for a long time, water has been often regarded as an unsuitable medium for organic reactions. We have, however, found that photo-chemical cyclopropanation of styrenes with diazo compounds or their precursors can be performed in micellar systems. COSMO-RS studies revealed that the reactivity correlates with the predicted critical micelle concentration (CMC), with higher CMC values delivering higher yields. [ABSTRACT FROM AUTHOR]

Herein, we report a photocatalytic method for the synthesis of 2‐quinolones under mild conditions by employing α‐diazo acetamide as substrates. The use of Eosin Y as a photocatalyst allows an economical and environmentally benign synthetic method. The process involves the generation of radicals from diazo compounds promoted by a visible‐light‐induced proton‐coupled electron transfer (PCET) mechanism. The method demonstrates a broad substrate scope to provide various aryl‐ and alkyl‐substituted 2‐quinolones. To support the proposed mechanism, a series of mechanistic experiments were conducted. [ABSTRACT FROM AUTHOR]

The metal-catalyzed carbenoid-based N–H insertions of α-stabilized diazo compounds and relative precursors serve as robust strategies for the formation of C–N bonds. However, carbenoid-based N–H insertions with aminopyridines are usually challenging due to the undesired coordination effect between the pyridine and the metal. Moreover, the coupling of donor/donor diazo compounds with amines remains challenging due to the instability and unavailability of donor/donor diazo compounds. Considering all these existing challenges, herein, a metal-free strategy is reported to achieve N–H insertions via coupling donor/donor diazo precursors (N-tosylhydrazones) with a plethora of amines including aminopyridines, anilines, aliphatic amines, and other nucleophiles such as imidazoles, pyrroles, and indoles. Expediently, β-amino esters are also afforded by using this mild strategy. The utility of this protocol is further demonstrated by the gram-scale synthesis and modifications of pharmaceuticals. Therefore, it is very clear that this metal-free approach uniquely tolerates a wide range of nucleophiles and opens a straightforward synthetic route to synthesize diverse value-added amines. [ABSTRACT FROM AUTHOR]

Asymmetric one‐carbon homologation or ring expansion of ketones with formal insertion of carbene intermediate, is a challenging but useful strategy to construct a complex skeleton. Sc(III) and chiral ligands have been employed in this regard. However, due to flexible conformations and a variety of stereo models, the origin of stereochemistry remains ambiguous. Density functional theory (DFT) calculations were carried out to explore the interactions that control the stereoselectivity of a Sc(III)‐catalyzed asymmetric homologation. The trans influence of counterions was found to affect the coordination mode of ketone to Sc(III), and consequently affect the stereoselectivity. [ABSTRACT FROM AUTHOR]

A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. [ABSTRACT FROM AUTHOR]

The development of stereoselective olefination using sulfur ylidederived vinyl carbenes with diazo esters and acetals is reported. Both reactions proceed through nucleophilic addition to electrophiles at the γ-position of an in situ-generated 2-alkoxy furan intermediate. The synthetic utility of the developed method is demonstrated by the total synthesis of rubrolide E. Detailed mechanistic investigations and quantum chemical calculations provide insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

α‐Silylated diazoalkynes are stabilized diazo compounds that can selectively react with carboxylic residues in buffered aqueous media. In‐situ fluoride induced desilylation increases this reactivity, leading to a very fast reaction. Application to the selective functionalization of RNase A, followed by post‐functionalization using click chemistry, is described. These new reagents expand the toolbox for native protein modification at carboxylic residues. [ABSTRACT FROM AUTHOR]

Trifluoroacetaldehyde N-tosylhydrazone used as a precursor for the in situ generation of CF3CHN2 by treatment with weak bases in safe concentration underwent [3+2] cycloaddition to electron deficient alkenes in the presence of N,N-diisopropylethylamine to give 5-(trifluoromethyl)pyrazolines in high yields. The reaction proceeded under mild conditions, tolerated a wide range of the substituents, and gave products promising for the drug design. The elaborated procedure avoided such drawbacks associated with the use of CF3CHN2 as volatility, toxicity, and explosion hazard. [ABSTRACT FROM AUTHOR]

Polyfluorinated substituents often enhance effectiveness, improve the stability within metabolic processes, and boost the lipophilicity of biologically active compounds. However, methods for their introduction into aliphatic carbon chains remain very limited. A potentially general route to integrate the fluorinated scaffolds into organic molecules involves insertion of fluorine‐containing carbenes into C(sp3)−H bonds. The electron‐withdrawing characteristics of perfluoroalkyl groups enhances the reactivity of these carbenes which should enable the functionalization of unactivated C(sp3)−H bonds. Curiously, it appears that use of perfluoroalkyl‐containing carbenes in alkane C−H functionalization is exceedingly rare. This concept describes photolysis, enzymatic catalysis, and transition metal catalysis as three primary approaches to C(sp3)−H functionalization by trifluoromethylcarbene and its homologues. [ABSTRACT FROM AUTHOR]

Environment-benign one-pot three-component cycloadditions of diazo compounds, nitrosoarenes and vinyl pyrimidines, or vinyl purines, or vinyl imidazoles, or vinyl triazoles or vinyl indole have been developed. This catalyst- and additive-free strategy could efficiently introduce the isoxazolidine skeleton into nucleoside analogues, oxazole molecules and indole derivatives to provide diverse classes of isoxazolidinyl pyrimidine nucleoside analogues, isoxazolidinyl purine nucleoside analogues, isoxazolidinyl imidazoles, isoxazolidinyl triazoles and isoxazolidinyl indole with moderate to good yields for most substrates. [ABSTRACT FROM AUTHOR]

A ruthenium‐catalyzed defluorinative annulation of 2‐alkenylanilines with α‐trifluoromethyl diazoester or diazoketones is described. The reaction has broad substrate scope, affording a range of gem‐difluorocyclobutane‐fused indolines in moderate to good yields with cis‐configuration. Mechanistic investigations indicate that the reaction proceeds through a sequential N−H insertion/C−F bond cleavage/[2+2] cycloadditon process. α‐Trifluoromethyl‐α‐diazo reagents serve as gem‐difluorinated C2 subunits by cleaving one C−F bond. [ABSTRACT FROM AUTHOR]

This article discusses the insertion reactions of α-diazo esters into carbon-carbon and carbon-halogen bonds using Lewis acid catalysts. The authors provide experimental results and mechanisms for these reactions, demonstrating their effectiveness in achieving desired outcomes. They also explore the scope of different substrates and potential applications of this methodology. The article discusses the use of α-diazo esters in various chemical reactions and proposes that this new strategy may have utility for other challenging reactions involving insertion into carbon-heteroatom bonds. [Extracted from the article]

Continuous flow chemistry has become the method of choice for the synthesis of toxic and explosive intermediates such as diazo reagents because they can be generated on demand and readily used, eliminating the need to handle hazardous materials. This inherent increase in safety makes it more feasible to use these reagents in day-to-day synthesis. Herein, we describe a continuous flow, metal-free, easy-to-use method for the preparation of semi-stabilized and unstabilized diazo reagents. The scope of the described continuous flow oxidation of hydrazones using a packed bed column with iodosylbenzene includes 13 semi-stabilized and 13 unstabilized diazo reagents in solution in dichloromethane while producing only 1 equivalent of water and iodobenzene as by-products. These otherwise difficult to access compounds are further reacted either in situ or at the reactor outlet to yield esters and ethers in good to excellent yields (47–96%). [ABSTRACT FROM AUTHOR]

Abstract Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β‐carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β‐carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo‐/enantio‐selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β‐carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products.

[Display omitted] Reaction of [(coe) 2 IrCl] 2 (coe = cyclooctene) with AgPF 6 , arene (toluene, p -xylene, mesitylene), and diphenylacetylene, followed by counter anion exchange to BARF–, gives cyclobutadiene iridium complexes [(C 4 Ph 4)Ir(arene)]BARF in 10–22% yield. Replacement of toluene in [(C 4 Ph 4)Ir(toluene)]BARF by various ligands (trimethyl-phosphite, 1,3,5-triaza-7-phosphaadamantane, tert -butyl isonitrile) provides access to the half-sandwich cyclobuta-diene iridium complexes [(C 4 Ph 4)Ir(L) 3 ]BARF. Complex [(C 4 Ph 4)Ir(toluene)]BARF in combination with [NBnEt 3 ]Cl catalyses the insertion reaction between phenyl diazoacetate and various amines. [ABSTRACT FROM AUTHOR]

Copper catalysts containing alkoxydiaminophosphine (ADAP) ligand catalyze the selective C3−H functionalization of unprotected indoles upon carbene transfer from donor‐acceptor diazo compounds, the N−H bond remaining unaltered during the transformation. Mechanistic studies, including DFT calculations, allows proposing the existence of two competitive pathways, none of them occurring through the formation of cyclopropane intermediates, at variance with previously reported systems. [ABSTRACT FROM AUTHOR]

The insertion or transfer of carbene using diazo compounds as a precursor is being used widely to synthesize/functionalize different classes of organic compounds. Different types of catalysts (e.g., transition metals, enzymes, Lewis acids, Brønsted acids) have significant roles in this context. Nevertheless, there is a high demand for "green", stable, cost-effective, and reusable catalysts for carbene insertion/transfer reactions. Herein, we report (for the first time) the application of carbon material (i.e., graphene oxide) as a catalyst in the carbene-transfer reaction using 3-diazo oxindole as a carbene precursor reacting with indoles to furnish biologically important 3,3′,3′′-trisindoles. The generality and robustness of the developed protocol was shown by employing different types of substitutions at the 3-diazo oxindole and indole which, in turn, provided 3,3′,3′′-trisindoles derivatives in good-to-excellent yield (61–91%). We revealed the utility of the developed protocol by synthesizing different biologically active molecules on the gram-scale. [ABSTRACT FROM AUTHOR]