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The skeletal editing of azaarenes through insertion, deletion, or swapping of single atoms has recently gained considerable momentum in chemical synthesis. Here, we describe a practical skeletal editing strategy using vinylcarbenes in situ generated from trifluoromethyl vinyl N‐triftosylhydrazones, leading to the first dearomative skeletal editing of pyrroles through carbon‐atom insertion. Furthermore, depending on the used catalyst and substrate, three types of peripheral editing reactions of pyrroles are also disclosed: α‐ or γ‐selective C−H insertion, and [3+2] cycloaddition. These controllable molecular editing reactions provide a powerful platform for accessing medicinally relevant CF3‐containing N‐heterocyclic frameworks, such as 2,5‐dihydropyridines, piperidines, azabicyclo[3.3.0]octadienes, and allylated pyrroles from readily available pyrroles. Mechanistic insights from experiments and density functional theory (DFT) calculations shed light on the origin of substrate‐ or catalyst‐controlled chemo‐ and regioselectivity as well as the reaction mechanism. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Over the past few decades, N‐sulfonyl hydrazones have been recognized as alternative precursors for hazardous diazo compounds in organic synthesis, allowing for diverse innovative and original chemical transformations that were otherwise difficult to achieve. This critical review summarizes the major advancements in the carbene chemistry of N‐sulfonyl hydrazones. The contents of this review are organized based on research conducted by leading scientists who have made significant contributions to this field. The individual carbene transfer reactions and their mechanisms, as well as the potential applications in the synthesis of natural products and complex bioactive molecules, are thoroughly discussed. [ABSTRACT FROM AUTHOR]

The skeletal ring expansion of heteroarenes through carbene insertion is gaining popularity in synthetic chemistry. Efficient strategies for heterocyclic ring expansion to access heterocycles containing a fluoroalkyl quaternary carbon center through fluoroalkyl carbene insertion are highly desirable because of their broad applications in medicinal chemistry. Herein, we report a general strategy for the dearomative one‐carbon insertion of azoles using fluoroalkyl N‐triftosylhydrazones as fluoroalkyl carbene precursors, resulting in ring‐expanded heterocycles in excellent yields with good functional‐group compatibility. The broad generality of this methodology in the late‐stage diversification of pharmaceutically interesting bioactive molecules and versatile transformations of the products has been demonstrated. [ABSTRACT FROM AUTHOR]

A silver‐catalyzed regioselective defluorinative 1,3‐dienylation of trifluoromethyl phenyl N‐triftosylhydrazones using homoallenols as 1,3‐dienyl sources provides a variety of α‐(di)fluoro‐β‐vinyl allyl ketones with excellent functional group tolerance in moderate to good yields. The reaction proceeds through a silver carbene‐initiated sequential etherification and Claisen type [3,3]‐sigmatropic rearrangement cascade. The synthetic utility of this protocol was demonstrated through the downstream synthetic elaboration toward diverse synthetically useful building blocks. [ABSTRACT FROM AUTHOR]

(Hetero)arenes continue to prove their indispensability in pharmaceuticals, materials science, and synthetic chemistry. As such, the controllable modification of biologically significant (hetero)arenes towards diverse more‐potent complex molecular scaffolds through peripheral and skeletal editing has been considered a challenging goal in synthetic organic chemistry. Despite many excellent reviews on peripheral editing (i. e., C−H functionalization) of (hetero)arenes, their skeletal editings via single atom insertion, deletion, or transmutations have received less attention in the review literature. In this review, we systematically summarize the state‐of‐the‐art skeletal editing reactions of (hetero)arenes using carbenes, with a focus on general mechanistic considerations and their applications in natural product syntheses. The potential opportunities and inherent challenges encountered while developing these strategies are also highlighted. [ABSTRACT FROM AUTHOR]

The construction of allylic quaternary sp3‐carbon centers has long been a formidable challenge in transition‐metal‐catalyzed alkyl‐allyl coupling reactions due to the severe steric hindrance. Herein, we report an effective carbene strategy that employs well‐defined vinyl‐N‐triftosylhydrazones as a versatile allylating reagent to enable direct assembly of these medicinally desirable structural elements from low‐cost alkane feedstocks. The reaction exhibited excellent site selectivity for tertiary C−H bonds, broad scope (>60 examples and >20 : 1:0 r. r.) and good efficiency, even on a gram‐scale, making it a convenient alternative to the well‐known Trost–Tsuji allylation reaction for the formation of alkyl–allyl bonds. Combined experimental and computational studies were employed to unravel the mechanism and origin of site‐ and chemoselectivity of the reaction. [ABSTRACT FROM AUTHOR]

Catalytic carbene transfer reactions are fundamental transformations in modern organic synthesis, which enable direct access to diverse structurally complex molecules. Despite diazo precursors playing a crucial role in catalytic carbene transfer reactions, most reported methodologies take into account only diazoacetates or related compounds. This is primarily because diazoalkanes, unless they contain a resonance stabilizing group, are more susceptible to violent exothermic decomposition. In this feature article, we present an alternative approach to carbene-transfer reactions based on the formation of highly electrophilic silver carbenes from N-sulfonylhydrazones, where the high electrophilicity of silver carbenes stems from the weak interaction between silver and the carbenic carbon. These precursors are readily accessible, stable, and environmentally sustainable. Using the strategy that employs highly electrophilic silver carbenes, it is possible to develop novel intermolecular transformations involving non-stabilized carbenes, including C(sp3)–H insertion, C(sp3)–C(O) insertion, cycloaddition, and defluorinative functionalization. The silver-catalyzed carbene transfer reactions described here have high efficiency, unusual reactivity, exceptional selectivity, and a reaction pathway that differs from typical transition metal-catalyzed reactions. Our research provided fundamental insight into silver carbene chemistry, and we hope to apply this mode of catalysis to other more general transformations, including asymmetric transformations. [ABSTRACT FROM AUTHOR]

The insertion of carbenes into the α-C–H bonds of ethers represents one of the most powerful approaches to access polysubstituted α-branched ethers. However, intermolecular carbene insertions remain challenging, since current approaches are generally limited to the use of toxic and potentially explosive α-diazocarbonyl compounds. We now report a silver-catalyzed α-C–H benzylation of ethers using bench-stable N-triftosylhydrazones as safe and convenient carbene precursors. This approach is well suited for both inter- and intramolecular insertions to deliver medicinally relevant homobenzylic ethers and 5–8-membered oxacycles in good yields. The synthetic utility of this strategy is demonstrated by its easy scalability, broad scope with valuable functional groups, high regioselectivity, and late-stage functionalization of complex oxygen-containing molecules. The relative reactivities of different types of silver carbenes and C−H bonds were also investigated by experments and DFT calculations. A state-of-the-art tool in synthetic organic chemistry is a rhodium diazocarbene species, which despite its flexibility, is derived from expensive and highly reactive species. Here the authors present a methodology for C–H benzylation of ethers via an analogous silver carbene species, obtained from a more common metal and a more stable starting material. [ABSTRACT FROM AUTHOR]

Hydrodefluorination is one of the most promising chemical strategies to degrade perfluorochemicals into partially fluorinated compounds. However, controlled progressive hydrodefluorination remains a significant challenge, owing to the decrease in the strength of C−F bonds along with the defluorination. Here we describe a carbene strategy for the sequential (deutero)hydrodefluorination of perfluoroalkyl ketones under rhodium catalysis, allowing for the controllable preparation of difluoroalkyl‐ and monofluoroalkyl ketones from aryl‐ and even alkyl‐substituted perfluoro‐alkyl ketones in high yield with excellent functional group tolerance. The reaction mechanism and the origin of the intriguing chemoselectivity of the reaction were rationalized by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Fluoroalkyl 1,2,3-triazoles have great potential as medicinal chemistry building blocks. However, only a few synthetic routes to these compounds are currently available. Herein, we report on a novel method to access 5-fluoroalkyl 1,2,3-triazoles from easily prepared bench-stable perfluoroalkyl N-mesylhydrazone (PFHZ-Ms), a reagent that can transform amines to 5 fluoroalkyl 1,2,3-triazoles via defluorinative [4 + 1] annulation. The simple reaction protocol can be applied to a variety of amines containing a range of functional groups, delivering 1,2,3-triazoles in good to excellent yield. The utility of this method was demonstrated in the late-stage modification of bioactive molecules. [ABSTRACT FROM AUTHOR]

We have described a simple, convenient, and high‐yielding one‐pot synthesis of novel azo chromene derivatives via a three‐component reaction of various azo aldehydes with dimedone and malononitrile using 10 mol% of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as catalyst and ethanol as solvent at reflux condition. All the synthesized compounds have been characterized using Fourier‐transform infrared spectroscopy (FT‐IR), 1H NMR, 13C NMR, and HR‐MS spectra and molecular docking was performed to explore new inhibitors of human placental aromatase cytochrome P450 and cyclooxygenase‐2 enzymes. Of all the compounds docked, compound (E)‐2‐amino‐4‐(4,4‐dimethyl‐2,6‐dioxocyclohexyl)‐6‐((3‐methoxyphenyl)diazenyl‐4H‐chromene‐3‐carbonitrile (4o) showed good binding affinity with the active site of human placental aromatase cytochrome P450 enzyme (PDB: 3EQM) with inhibition constant (Ki) 1.66 nM and compound 4o also showed good binding affinity with the active site of cyclooxygenase‐2 enzyme (PDB: 6COX) with inhibition constant (Ki) 367.17 pM. In vitro anti‐cancer activity studies against MCF‐7 cells were also performed for compounds 4o, anastrozole and celecoxib. Compound 4o showed an effective cytotoxicity at 19.8 μg/ml compared to anastrozole and celecoxib (24.7 and 26.2 μg/ml). [ABSTRACT FROM AUTHOR]

We have synthesized a new series of 1,8-dioxo-octahydroacridin-4-methylbenzenesulfonamide scaffolds via the one-pot multicomponent condensation reactions of diverse aryl aldehydes and p-toluenesulfonyl hydrazide with dimedone or 1,3-cyclohexanedione in glacial acetic acid as an efficient and cheaper reaction medium. The progress of the reaction was monitored by thin layer chromatography and the recrystallized products were analyzed by FT-IR, 1H, 13C NMR and mass spectral techniques. [ABSTRACT FROM AUTHOR]

Despite the growing importance of volatile functionalized diazoalkanes in organic synthesis, their safe generation and utilization remain a formidable challenge because of their difficult handling along with storage and security issues. In this study, we developed a bench‐stable difluoroacetaldehyde N‐triftosylhydrazone (DFHZ‐Tfs) as an operationally safe diazo surrogate that can release in situ two low‐molecular‐weight diazoalkanes, diazoacetaldehyde (CHOCHN2) or difluorodiazoethane (CF2HCHN2), in a controlled fashion under specific conditions. DFHZ‐Tfs has been successfully employed in the Fe‐catalyzed cyclopropanation and Doyle–Kirmse reactions, thus highlighting the synthetic utility of DFHZ‐Tfs in the efficient construction of molecule frameworks containing CHO or CF2H groups. Moreover, the reaction mechanism for the generation of CHOCHN2 from CF2HCHN2 was elucidated by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

In recent years, radical C–C bond cleavage reactions have been increasingly understood and used to perform transformations that complement traditional ionic processes. However, to date radical C–C bond cleavage/functionalization reactions have not been the subject of a dedicated review. Herein we summarize the most recent and significant developments in the radical activation and functionalization of carbon–carbon bonds, with an emphasis on both synthetic outcomes and reaction mechanisms, and highlight how these radical C–C bond cleavage reactions enable challenging transformations. [ABSTRACT FROM AUTHOR]

Abstract: A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C−C or C−H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)−C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C−C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C−H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity. [ABSTRACT FROM AUTHOR]

Abstract: An efficient one‐pot multicomponent double Michael addition strategy was developed for the synthesis of novel curcumin derivatives using 1,4‐diazabicyclo [2.2.2] octane (DABCO) as the catalyst. Selected compounds (E)‐4,4′′,5′‐trihydroxy‐6′‐(3‐(4‐hydroxy‐3‐methoxyphenyl)acryloyl)‐3,3′′‐dimethoxy‐3′,4′‐dihydro‐[1, 1′:3′, 1′′‐terphenyl]‐2′,2′(1′H)‐dicarbonitrile (4 k) and (E)‐ethyl 2′‐cyano‐4′′,5′‐dihydroxy‐6′‐(3‐(4‐hydroxy‐3‐methoxyphenyl)acryloyl)‐3′′‐methoxy‐4‐methyl‐1′,2′,3′,4′‐tetrahydro‐[1, 1′:3′, 1′′‐terphenyl]‐2′‐carboxylate (6 j) were evaluated for their in‐vitro anticancer activities against human breast cancer cells (MCF‐7) and human normal breast cells (HBL 100) and found to show effective cytotoxicity on MCF‐7 cells and less cytotoxicity on HBL 100 cells than simple curcumin. In addition, molecular docking studies helped to rationalize anti‐apoptotic Bcl‐2 binding of all the synthesized compounds and revealed that the docking of compounds 4 k and 6 j with Bcl‐2 was more potent compared to curcumin. [ABSTRACT FROM AUTHOR]

A silver-catalyzed tandem carbon-carbon triple bond hydroazidation, radical addition, and cyclization of biphenyl acetylene is described under mild conditions, leading to the formation of 6-methyl sulfonylated phenanthridines in good yields. In this novel cascade reaction, most of the atoms are incorporated into the product without cleavage of the C·C bond. Mechanistic studies suggest the reaction should proceed through an iminyl radical reactive intermediate. [ABSTRACT FROM AUTHOR]

In this paper, a series of bis(2,3-dihydroquinazolin-4(1 H)-one) derivatives ( 4a-i, 10a-k) were synthesized by the one-pot pseudo-five-component reaction of isatoic anhydride with aromatic aldehydes and aromatic amines under reflux in glacial acetic acid. The synthesized compounds were screened for their antioxidant properties using the DPPH radical scavenging method. Compounds 4i and 10h showed potent radical scavenging activities at 20 $$\upmu \hbox {g}/\hbox {mL}$$ compared to BHA and ascorbic acid. The anticancer activity of compound 4f was evaluated against human breast cancer cell line (MCF 7), and the observed $$\hbox {GI}_{50}$$ was found to be 11.4 $$\upmu \hbox {m}$$ . The redox behaviour of some analogues was evaluated by cyclic voltammetric methods, and it is found that compound 7d possesses the maximum redox potential. Graphical Abstract : [ABSTRACT FROM AUTHOR]

The title chromenes are efficiently prepared by Knoevenagel condensation of active methylene compounds with aromatic azosalicylaldehydes using piperidine as catalyst followed by nucleophilic addition of the phenolic hydroxyl group to the carbonyl group of one of the ester groups. [ABSTRACT FROM AUTHOR]

A simple strategy is reported for the rapid synthesis of novel tricyclic azo group containing eight membered dibenzo[b,f][1,5]oxazocin-6-ones. [ABSTRACT FROM AUTHOR]

An abstract of the article "Metal Free Organic Transformation: Cyanuric Chloride Catalyzed Synthesis of 5 Substituted-1H-tetrazoles" by P. Sivaguru, P. Theerthagiri and A. Lalitha is presented.

via condensation of dimedone with aromatic aldehydes (13 examples) [ABSTRACT FROM AUTHOR]