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The prominence of saturated N -heterocycle motifs in pharmaceuticals is undeniable. Challenges associated with the alkylation of saturated N -heterocycle scaffolds to efficiently access new drug analogues are hampered by synthetically laborious routes. Stereocontrolled alkyl-substitutions onto saturated N -heterocycles are particularly difficult to access in high yields by traditional synthetic methods. Alternatively, C–H bond functionalization provides a new and powerful synthetic avenue by directly and selectively functionalizing/alkylating/ arylating the abundantly available C–H bonds of saturated N -heterocycles. This review highlights complementary methods for directly activating and functionalizing C–H bonds of saturated N -heterocycles chemo-, regio-, and or stereoselectively to access alkylated products. This synthetic challenge has required catalyst development to access useful N -heterocyclic building blocks or for late-stage functionalization. Early transition metal, late transition metal, photoredox, and electrochemical methods are discussed. The selective functionalization of α, β, and γ C–H bonds to form new C–C, C–N, C–O, and C–B bonds is presented. 1 Introduction 2 Early Transition Metal Catalyzed α-Alkylation 3 Late Transition Metal Catalyzed α-Functionalization 4 Photoredox-Catalyzed α-Functionalization 5 Electrochemical α-Functionalization 6 C–H Functionalization of β and γ C–H Bonds 7 Conclusions/Outlook [ABSTRACT FROM AUTHOR]

The present study demonstrates biogenically synthesized copper-oxalate supported on iron oxide (Fe3O4) and its implementation for pharmaceutically important quinoline and quinazoline synthesis. The formation of a new catalyst was confirmed by Field emission scanning electron microscope (FE-SEM) and Brunauer–Emmett–Teller (BET) analysis that displayed a spherical shape with a surface area of 18.407 m2 g−1, and an active metal concentration of 12.02 w/w%. The dual role of choline azide as a green solvent as well as a nitrogen source is demonstrated and a series of quinoline and quinazoline derivatives were synthesized in good to excellent yield. Importantly, catalyst recyclability, mechanistic investigations, control experiments, and reaction economy highlight the importance of methodology. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Two reaction modes for metal‐free [3 + 2] cyclization of N‐aminopyridinium derivatives with β‐alkoxyvinyl trifluoromethylketones have been described through selective C—O or C—O/C—C bond cleavage. This strategy can also be extended to the [3 + 2] cyclization of N‐aminopyridinium derivatives with enaminones and bromoalkynes. A broad range of N‐aminopyridinium, N‐aminoquinolinium, and N‐aminoisoquinolinium salts are well tolerated, enabling the divergent synthesis of trifluoroacylated, non‐substituted, acylated, and brominated pyrazolo[1,5‐a]pyridine derivatives (62 examples). [ABSTRACT FROM AUTHOR]

Triarylamines are frequently employed as electron donor functional groups in a variety of organic electronic materials. We herein report the synthesis and in‐depth characterisation of aza‐analogues of fully bridged triarylamines, consisting of 5‐, 6‐ and 7‐membered rings. The impact of nitrogen doping and π‐extension on the structural, electronic and optical‐properties of these contorted heteroaromatic PAHs is thoroughly investigated and paves the way for an improved understanding of the structure‐property relationships. [ABSTRACT FROM AUTHOR]

Herein, we have demonstrated the design and synthesis of a novel Ni‐immobilized MOF as heterogeneous catalyst for the dehydrogenation of N‐heterocycles. A series of five and six‐membered N‐heteroarenes bearing one or more heteroatoms were synthesized in up to 98 % yield (>33 examples). Late stage functionalization to the synthesis of β‐glucuronides inhibitor, antimalarial drug quinine, and the nonsteroidal anti‐inflammatory drug (NSAID) indomethacin were obtained under milder reactions conditions. A series of mechanistic studies revealed the detection of H2 and H2O2 during the progress of the reactions and suggested the involvement of enamine‐imine intermediate species for sequential dehydrogenation. Detailed characterization of the fresh catalyst and reused catalyst were performed using SEM, TEM, BET, PXRD, and EDX elemental mappings. The catalyst could be recycled up to four‐times without much loss in catalytic activities. In‐situ formed defects, pore size enlargement and additional Lewis acid sites within catalyst nanocrystals assisted in attaining high activity and selectivity to N‐heteroarenes. [ABSTRACT FROM AUTHOR]

This manuscript reports a novel method for the direct iodination of the C‐4 pyrazole ring generated in situ by the reaction of 1,1,3,3‐tetramethoxypropane and various hydrazines. In this approach, potassium iodate (KIO3) is used as the iodinating agent and (PhSe)2 is used as catalysts under acidic conditions. This protocol provides a convenient method for the efficient synthesis of 4‐iodo‐1‐aryl‐1H‐pyrazoles, valuable intermediates for several different coupling reactions. [ABSTRACT FROM AUTHOR]

Indolizines and imidazo[1,2‐a]pyridines are commonly found in natural products, synthetic drugs, and bioactive molecules. These two types of derivatives possess good antibacterial, antiparasitic, anticancer activities, and so on. The functionalization of indolizines and imidazo[1,2‐a]pyridines has always been a hot topic in organic chemistry research and has made significant progress. In recent years, our group has been dedicated to developing diverse synthetic methods for the preparation of such important compounds. 1) We have developed diverse C−H functionalization reactions for efficient modification of the parent indolizines and imidazo[1,2‐a]pyridines. 2) A variety of cycloaddition reactions were established for the construction of indolizine and imidazo[1,2‐a]pyridine derivatives from simple raw materials. 3) We have developed intriguing deconstruction‐functionalization reactions of indolizines, enabling the reorganization of heterocyclic frameworks. This paper outlines our group's latest advancements in constructing structurally diverse indolizine and imidazo[1,2‐a]pyridine derivatives. We hope that this work will offer valuable insights and inspiration for the ongoing research in the field of N‐heterocyclic compounds. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: α‐Azaarene quaternary carbon centers are prevalent in drug molecules, making the development of efficient synthetic approaches of great interest. Herein, we describe an unprecedented method for constructing α‐all‐carbon quaternary carbon‐centered azaarenes by employing photocatalytic reductive coupling of various 2,2‐disubstituted cycloproarylketones with readily available cyanoazaarenes. The reaction proceeds with high efficiency, displaying excellent compatibility with various functional groups and demonstrating high chemo‐ and regioselectivity. Mechanistic investigations suggest that consecutive photo‐induced electron transfer (ConPET) plays a crucial role in the formation of photocatalyst with greater reducing capability, ultimately enabling the direct reductive conversion of unreactive π‐bonds under mild and transition‐metal‐free conditions. [ABSTRACT FROM AUTHOR]

The discovery of structurally unique scaffolds entities with increased complexity and balanced physicochemical properties has the potential to allow synthetic chemists to exploit areas of chemical space that were previously inaccessible. Among the different strategies employed for generating N‐heterocycles, cyclization and cycloaddition reactions represent a valuable synthetic tool. The purpose of this minireview is to summarize the recent advances (2009‐present) from our laboratory on the generation of intriguing five‐, six‐ and seven‐membered mono‐ or poly‐heterocyclic architectures (linear, fused and spiro) employing 1,2‐diaza‐1,3‐dienes (DDs) as key synthons. [ABSTRACT FROM AUTHOR]

Comprehensive Summary A variety of 3‐nitroindazoles and 3‐aminoindazoles were prepared in good to excellent yields with high regioselectivity through TBN‐mediated nitration at the C3‐position of indazoles under the air conditions and sequential reduction. Mechanistic studies revealed that TBN played crucial roles to produce •NO2 radical source in the presence of air conditions and C3‐nitration of indazoles was initiated by N1‐nitration and sequential migration of NO2 group to C3‐position. Moreover, this method could be easily applied in the gram scalable synthesis of ibuprofen and ciprofibrate‐derived 3‐aminoindazoles. The present method highlights air as mild oxidant, metal‐free radical nitration of indazole, N—N bond formation and cleavage, and late‐stage modification of drugs. [ABSTRACT FROM AUTHOR]

We describe the synthesis and computational investigation of N‐heterocycle‐substituted hexa‐peri‐hexabenzocoronenes (HBCs). Following our method for the preparation of thioether‐substituted HBCs, we prepared pyrrole‐, indole‐, carbazole‐, and 1H‐benz[g]indole‐substituted HBCs from the corresponding fluorinated precursors under microwave irradiation. A series of polysubstituted benzoindole‐HBCs with windmill architectures was also synthesized using the polyfluorinated HBC analogs, and the substituent effects on the electronic properties of the HBC core were investigated. Similar to the thioether substituted HBCs, the nature of the heterocycle does not influence the optoelectronic properties of the HBC core. The attachment of multiple benzoindole substituents leads to a bathochromic shift of the absorption and emission spectra, comparable to our previous studies. Due to the circular arrangement of the benzoindole moiety, the attachment of multiple substituents results in the presence of multiple conformers at room temperature. The rotation barrier can be overcome by heating the compounds to 323–333 K. Additionally, the investigation of the relaxed geometries shows two π‐stacking motifs within the conformers. [ABSTRACT FROM AUTHOR]

As nitrogen analogues of iron‐oxo species, high‐valent iron‐imido species have attracted great interest in the past decades. FeV‐alkylimido species are generally considered to be key reaction intermediates in Fe(III)‐catalyzed C(sp3)─H bond aminations of alkyl azides but remain underexplored. Here, it is reported that iron‐corrole (Cor) complexes can catalyze a wide range of intramolecular C─H amination reactions of alkyl azides to afford a variety of 5‐, 6‐ and 7‐membered N‐heterocycles, including alkaloids and natural product derivatives, with up to 3880 turnover numbers (TONs) and excellent diastereoselectivity (>99:1 d.r.). Mechanistic studies including density functional theory (DFT) calculations and intermolecular hydrogen atom abstraction (HAA) reactions reveal key reactive FeV‐alkylimido intermediates. The [FeV(Cor)(NAd)] (Ad = adamantyl) complex is independently prepared and characterized through electron paramagnetic resonance (EPR), resonance Raman (rR) measurement, and X‐ray photoelectron spectroscopy (XPS). This complex is reactive toward HAA reactions with kinetic isotope effects (KIEs) similar to [Fe(Cor)]‐catalyzed intramolecular C─H amination of alkyl azides. [ABSTRACT FROM AUTHOR]

Efficient approaches toward the synthesis of quinazolines and dihydroisoquinolines have been developed through copper‐catalyzed aerobic oxidative dehydrogenation of N‐heterocycles. The dehydrogenation was achieved through copper‐catalyzed aerobic oxidative dehydrogenation and azodicarboxylate esters‐mediated dehydrogenation of amines. Azodicarboxylate esters could be regenerated from copper‐catalyzed dehydrogenation of corresponding hydrazodicarboxylate esters, which made this catalytic dehydrogenation process more efficient and reactive. [ABSTRACT FROM AUTHOR]

Nitrogen‐heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C−H amination reactions furnish unconventional and straightforward approaches for the construction of C−N bonds. Yet, most of the known methods rely on precious metal catalysts. Herein we report a site‐selective intermolecular C(sp3)−H amination of N‐heterocycles, catalyzed by inexpensive FeCl2, which allows the functionalization of a wide range of pharmaceutically relevant cyclic amines. The C−H amination occurs site‐selectively in α‐position to the nitrogen atom, even when weaker C−H bonds are present, and furnishes Troc‐protected aminals or amidines. The method employs the N‐heterocycle as limiting reagent and is applicable to the late‐stage functionalization of complex molecules. Its synthetic potential was further illustrated through the derivatization of α‐aminated products and the application to a concise total synthesis of the reported structure for senobtusin. Mechanistic studies allowed to propose a plausible reaction mechanism involving a turnover‐limiting Fe‐nitrene generation followed by fast H atom transfer and radical rebound. [ABSTRACT FROM AUTHOR]

The acceptorless dehydrogenation reaction is a sustainable and atom‐economical methodology in organic synthesis, resulting in the byproducts of only hydrogen or water. Herein, a robust Co−Si/CN catalyst (derived from ZIF@SiO2 composite) has been synthesized through a one‐step assembly process via pyrolysis and etching. This catalyst has been employed for the acceptorless dehydrogenative coupling of 2‐aminoalcohols with secondary alcohols, enabling efficient conversion of various substrates into desired quinoline or pyridine derivatives with a yield of up to 94 %. [ABSTRACT FROM AUTHOR]

Site‐selective amination of N‐heterocycles is an interesting topic in organic synthesis and drug discovery. We herein present a method for the vicarious‐type nucleophilic amination of azine N‐oxides and cyclic iminoamides using iminyl anions, readily generated from organic azides under basic conditions. The plausible reaction mechanism involving nucleophilic aromatic substitution by iminyl anions is elucidated by a series of mechanistic investigations. [ABSTRACT FROM AUTHOR]

A method for synthesizing pyrimido[1,2‐a]indol‐4‐ol heteroarenes via a Cp*Rh(III)‐catalyzed cascade C−H activation/annulation strategy employing N‐methoxyindoleamides and isoxazolones is developed. Also, a framework of 3‐methoxy‐2,3‐dihydro‐[1,3,5]triazino[1,2‐a]indole‐4,10‐dione was successfully synthesized via a Cp*Rh‐catalyzed C−H activation/annulation/oxidation reaction between N‐(methyloxy)‐1H‐indole‐1‐carboxamide and isoxazolones. These reactions demonstrated the suitability of several substrates, compatibility with numerous functional groups, and mild reaction conditions. Preliminary mechanistic investigations have been completed. [ABSTRACT FROM AUTHOR]

Nitrogen‐containing heterocycles represent fundamental components found in a myriad of natural compounds, pharmaceuticals, tailored bioactive substances, and agrochemicals. In recent decades, the field of synthetic chemistry has prioritized these compounds, directing considerable research endeavour toward developing efficient and concise methodologies for their synthesis. Consequently, there is a growing interest in pioneering novel synthetic approaches to fabricate these immensely coveted structural motifs. Transition metal‐catalyzed reactions leveraging solvents as carbon (C1) synthons offer notable advantages, including streamlined processes, enhanced atom economy, and environmental sustainability. This review sheds light on the recent advancements in the utilization of collective solvents such as methanol (alongside other alcohols), N,N‐dimethylethanolamine (DMEA), and triethylamine (TEA) (in conjunction with other amines), tetrahydrofuran (THF), toluene, dichloromethane (DCM), dimethyl sulfoxide (DMSO), and dimethylformamide (DMF) as C1 synthons, serving as foundational units for the synthesis of N‐heterocycles, including quinazolinone, quinazoline, quinoxaline, pyridine, and pyrimidine, among others. Various reaction conditions employing diverse transition metals, coupling partners, and solvents as carbon synthons or reagents, as reported in the literature, have been explored. [ABSTRACT FROM AUTHOR]

Quinoline is one of the most important nitrogen containing heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. Specifically, several quinoline based renowned antimalarial agents have served the mankind for several past decades and showed strong potential applications in other field also. 3‐Formyl‐quinoline is a versatile precursor which can be transformed using several easy methods into a wide range of biologically valuable scaffolds. The exploration of 3‐formyl‐quinolines have gained much more attention to medicinal chemists in the field of drug discovery to design and synthesize new fused/tethered quinolines as potent therapeutical agents. This manuscript summarizes the reports (from 2011 to 2023) which showing the synthetic potential of quinoline‐3‐carbaldehydes. [ABSTRACT FROM AUTHOR]

Organophosphorothioates are organic molecules containing sulfur and phosphorus, with significant biological activity and physicochemical properties, widely used in organic synthesis, medicinal chemistry, and the agrochemical industry. In particular, many phosphorothioates display a variety of biological activities, such as antifungal, antibacterial, anti‐parasite, anticancer, and so on. Traditionally, the synthesis of phosphorothioates has mainly relied on indirect methods involving the construction of S−P bond. In recent years, direct phosphorothiolation has gained attention as a reliable and rapid method for introducing the −S−P(O)(OR)2 group into parent molecules. This article reviews the latest advances in direct phosphorothiolation reactions, categorized based on the different sources of the −S−P(O)(OR)2 group. [ABSTRACT FROM AUTHOR]

The relevance of the asymmetric Biginelli reaction (ABR) has been increased in this century, due to the pharmacological application of its products. This review focuses predominantly on articles published in the period from 2015 to 2024 on asymmetric synthetic advances in the formation of dihydropyrimidinones (DHPMs), dihydropyrimidinethiones (DHPMTs), and related compounds. The relevant bibliography on general processes in the Biginelli reaction and some methods of separation of isomers have also been referenced. [ABSTRACT FROM AUTHOR]

Hydrogenation of N‐heteroarenes to saturated N‐heterocycles is an important reaction in organic synthesis. Hydrogen is a green reducing reagent and has been widely applied in industrial production. The development of an appropriate catalyst to realize hydrogenation at low pressure and temperature is desired. In this study, we developed a cobalt‐based catalyst derived from ZIF‐67 that exhibits high activity for N‐heteroarene hydrogenation under 5–20 bar hydrogen, which is a relatively low pressure as compared to reported catalytic systems. This nano‐cobalt catalyst shows broad substrate scope and can be reused without obvious activity loss. [ABSTRACT FROM AUTHOR]

The building of N-heterocyclic cores endures an influential area of research due to their ubiquitous presence in natural products, agrochemicals, and small bioactive molecules. Over the past two decades, the synthesis of N-heterocycles via C-H activation comes out as a dominating synthetic protocol in atom-economic manner. The creation of C-C/C-N bonds acts as a key determining step for the building of nitrogen-based heterocycles via direct C-H activation protocol, which could serve as a fascinating concept. In recent years, Group 9 (Co, Rh & Ir) transition metal emerged as a robust catalytic system for the development of valuable N-heterocyclic scaffolds among other transition metals due to their mild reaction conditions, high reactivity, and functional group tolerance. A diverse type of arenes such as anilines/anilides, benzamides, hydrazones, ketoximes, benzylamine, and N-aryl nitrones were subjected to the C-H bond activation for the annulation reaction. Moreover, unsaturated compounds such as alkyne and olefin as coupling partners are again the most used companions for the same purpose, i.e., formation of N-heterocycles. Therefore, this review centers on the up-to-date reports on N-heterocycles synthesis by implementing alkynes and olefins as coupling partners through Group 9 transition metals' catalysis. The methodologies will be based on the coupling of alkynes and olefin, which preferably react in an intermolecular fashion. The scope, limitation, and mechanistic investigation of the Group 9 metal-activated C-H functionalization for the access of N-containing heterocycles with unsaturated reacting partners are the primary focus of the current review. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of substituted ß-homoprolines using rhodium catalysis. ß-Homoproline is a variant of ¿-proline and is found in natural products and pharmaceuticals. The article describes the development of a new method for synthesizing ß-homoprolines, which involves the cyclization of isoxazolidin-5-ones using a rhodium catalyst. The authors demonstrate the scope and limitations of this method and discuss the downstream transformations that can be performed on the resulting ß-homoprolines. Overall, this research provides valuable insights into the synthesis and potential applications of ß-homoprolines. [Extracted from the article]

A great deal of attention has been received on developing N‐heterocyclic compounds due to their ambitious biological activities. Many of them are essential footstep to the development and discovery of new drugs. Imidazole/benzimidazole and quinazoline are essential pharmacologically active N‐heterocycles, and one of the molecular framework built up from their combination, imidazo/benzimidazo[1,2‐c]quinazoline, is of great attention in terms of synthesis, reactions, and medicinal applications. The positional variation of hetero N‐atoms and the functional groups acting as substituents in the main scaffold have a direct impact on the properties of imidazo/benzimidazo[1,2‐c]quinazolines. In addition to its physiological activities, this moiety is useful for electrical conductivity, molecules/ions sensing, coordination complex and coordination polymer (CP) formation, and their diverse applications. The major objective of this review is to highlight various synthetic approaches for imidazo/benzimidazo[1,2‐c]quinazolines motif since 2000. Toxicant‐free reaction conditions and the use of an extensive range of inexpensive substrates are two of the main practical benefits of the protocol in accomplishing the sustainable development goals. [ABSTRACT FROM AUTHOR]

Molybdenum‐based efficient and broadly applicable catalytic system is presented for the dehydrogenative coupling of γ‐/β‐amino alcohols with ketones. In particular, complex Mo(CO)6 in combination with Xantphos and t‐BuOK as base provides direct synthesis of structurally diverse quinoline, pyridine, and pyrrole compounds (total 55 examples) with isolated yields up to 92%. Low catalyst loading, cost‐effective, and high catalytic activities with high tolerance to stand with diverse functional groups are additional features of these molybdenum catalysts exhibiting high efficacy to replace the precious metal catalysts such as ruthenium and iridium. Furthermore, the DFT and experimental studies were explored for the reaction mechanism which can assist in broadening the scope of the molybdenum catalysts for different transformation reactions. [ABSTRACT FROM AUTHOR]

N‐Heterocyclic compounds, in particular, quinolines and quinazolines are frequently used in medicinal chemistry. Therefore, the direct and clean synthesis of these valuable scaffolds has been a great interest for many years. 2‐Aminobenzyl alcohols as an alternative reactant instead of unstable and expensive 2‐aminobenzaldehydes can be used in the construction of N‐fused heterocycles including quinolines, quinazolines, oxazines, thiazines, selenazines, imidazoles, diazepines, etc. In this review article, we have discussed recent developments in the use of 2‐aminobenzyl alcohols in the synthesis of diverse heterocycles. [ABSTRACT FROM AUTHOR]

A DBU‐promoted [3+2] cyclization/retro‐Mannich cascade reaction of N‐aminoisoquinolinium and N‐aminoquinolinium derivatives with para‐quinone methides has been established, employing a C=C double bond cleavage. A broad range of N‐aminoquinolinium salts, N‐aminoisoquinolinium salts, and para‐quinone methides are well tolerated, providing the corresponding rearrangement products. Moreover, scaled‐up reactions and diverse derivatizations of the products were also investigated and discussed. [ABSTRACT FROM AUTHOR]

An efficient and green synthesis of tetramethyl‐10‐(phenylamino)‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione derivatives has been achieved from various substituted aryl aldehydes, 5,5‐dimethyl‐3‐(2‐phenylhydrazinyl)cyclohex‐2‐enone and dimedone in aqueous ethanol medium. Environment‐friendly reaction, excellent yields, operational simplicity and shorter reaction times are the significant features of the present protocol. All the synthesized compounds were characterized by various spectroscopic techniques and X‐ray crystal diffraction studies. [ABSTRACT FROM AUTHOR]

Indoline‐fused polycyclic scaffolds are virtually universal in biological and pharmaceutical. Here we demonstrate a facile electrooxidative cascade cyclization for indoline‐based derivatives, employing amidyl radicals with ynones under mild conditions. The efficient method enables the formation of two new C−N and C−C bonds in a single step with high regioselectivity. Various indoline‐based tetracyclic 6/5/6/6 skeletons can be achieved through a biscyclization/dehydrogenation cascade process. Additionally, this electrochemical strategy proceeds in a sustainable metal‐ and oxidant‐free condition, with H2 being the solely byproduct. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Heterodienes in organic synthesis," discusses the chemistry and applications of heterodienes in organic synthesis. Heterodienes are vinylogous systems that have unique reactivity and structure. They are commonly used in reactions such as Michael addition, cycloadditions, annulations, and cascade reactions. Heterodienes are also involved in the biosynthesis of natural compounds and can be used in bioconjugation chemistry. The article includes research on specific types of heterodienes, such as azoalkenes and nitroso- and nitroalkenes, and their reactions with various nucleophiles. The authors conclude that the chemistry of heterodienes is an exciting and challenging research area with many more discoveries to be made. [Extracted from the article]

Comprehensive Summary: The Pd‐catalyzed dipolar cycloaddition represents a significant synthetic strategy for the construction of useful heterocyclic compounds. This study developed the dipolar [4+2] and [6+2] cycloaddition reactions of benzo[d]isothiazole 1,1‐dioxides (BDs) leading to the synthesis of BD‐fused 1,3‐oxazinane and 1,3‐oxazocane derivatives, respectively. In particular, the synthesis of BD‐fused 1,3‐oxazinanes demonstrated regio‐ and enantioselective characteristics, resulting in products with good yields, enantioselectivity and regioselectivity (if applicable). Furthermore, the [6+2] cycloaddition reaction developed in this work represented the first strategy for the synthesis of medium‐sized ring compounds based on BDs. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The azepine ring is a prominent structural scaffold in biologically significant molecules. In this study, we present a Ni(II)‐catalyzed asymmetric difunctionalization of alkynes, involving intermolecular regioselective arylation and intramolecular nitrile addition, enabling the synthesis of enantioenriched azepine derivatives. This reaction simultaneously installs an all‐carbon quaternary stereocenter and introduces an unprotected imine functionality, showing great promise for subsequent transformations. The reaction exhibits good tolerance toward various functional groups, resulting in high yields and enantioselectivities. The synthetic utility of this methodology is further demonstrated through gram‐scale synthesis and product derivatization. This research offers an efficient approach to the synthesis of seven‐membered nitrogen heterocycles. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A convenient approach for the construction of 2‐aminobenzothiazoles via I2‐catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed. The present approach starts from simple and readily available starting materials, affording a series of 2‐aminobenzothiazoles in up to 89% yields under metal‐free conditions. In this work, C—H/N—H functionalization was achieved and multiple C‐hetero bonds were successfully constructed in one pot. [ABSTRACT FROM AUTHOR]

Porous organic polymers (POPs), and especially covalent triazine frameworks (CTFs), are being developed as the next generation of metal‐free heterogeneous photocatalysts. However, many of the current synthetic routes to obtain these photoactive POPs require expensive monomers and rely on precious metal catalysts, thus hindering their widespread implementation. In this work, a range of POPs was synthesized from simple unfunctionalized aromatic building blocks, through Lewis acid‐catalyzed polymerization. The obtained materials were applied, for the first time, as heterogeneous photocatalysts for the aromatization of N‐heterocycles. With the use of the most active material, denoted as CTF‐Pyr, which consists of photoactive pyrene and triazine moieties, a wide range of pyridines, dihydroquinoline‐5‐ones, tetrahydroacridine‐1,8‐diones and pyrazoles were obtained in excellent yields (70–99 %). Moreover, these reactions were carried out under very mild conditions using air and at room temperature, highlighting the potential of these materials as catalysts for green transformations. [ABSTRACT FROM AUTHOR]

This article explores the synthesis of N-arylated triazole derivatives using ligand-free copper catalysts. The authors optimize the reaction conditions and find that using CuCl as the catalyst, K3PO4 as the base, and DMF as the solvent yields the highest product yield. The study also investigates the substrate scope and finds that certain substitutions lead to higher yields. This research provides valuable insights into the synthesis of important compounds with potential pharmaceutical applications. The article acknowledges the support of the National Institute of Education, Singapore. [Extracted from the article]

Quinazolin-4(3H)-one structures are highly valued in synthetic chemistry due to their incorporation into diverse natural products and drug molecules. Here, we present a new approach for constructing quinazolin-4(3H)-ones utilizing the reactive N-sulfonoketenimines, generated in situ from terminal alkynes and sulfonyl azides and 2-aminobenzamides in the presence of CuI and Et3N. The reaction proceeded smoothly in MeCN at room temperature to afford the target compounds in good efficiency and amenable to gram-scale synthesis. [ABSTRACT FROM AUTHOR]

In this research, we present an innovative and eco‐friendly methodology for the synthesis of a diverse array of 2,3‐dihydroquinazolin‐4(1H)‐ones, featuring the use of catalytic N‐Bromosaccharin (NBSac). This novel approach is not limited to just one product; it extends to the efficient synthesis of quinazolin‐4(3H)‐ones by harnessing visible light alongside stoichiometric N‐Bromosaccharin (NBSac) as a multifunctional heterogeneous oxidant. By uniting cyclocondensation and oxidation into a one‐pot sequential process, direct access to quinazolin‐4(3H)‐ones is achieved. The developed protocol is characterized by its user‐friendliness, metal‐free operation, wide applicability across diverse substrates, and the ability to recycle the catalyst, making it an appealing and sustainable method for quinazolinone synthesis. [ABSTRACT FROM AUTHOR]

Borrowing hydrogen (BH) has reached a wide attention from the chemistry community as a new opportunity to construct efficiently C−N bond (as well as C−C or C−S bond). This straightforward strategy is usually supported by relevant organometallic catalysts, involved in the dehydrogenation‐reduction processes. This concept highlights specifically the application of the borrowing hydrogen to the preparation of saturated aza‐heterocycles (piperidines, pyrrolidines and piperazines) extensively present in high‐added value molecules of pharmaceutical industry over the last 40 years using homogenous catalysis in particular. A focus will be given to the appropriate metals (Ru, Ir and more recently earth‐abundant metals) used for this transformation. An extension to chiral induction in order to prepare enantiopure N‐heterocycles will be also reported. [ABSTRACT FROM AUTHOR]

Skeletal editing of N‐heterocycles has recently received considerable attention, and the introduction of boron atom into heterocycles often results in positive property changes. However, direct enlargement of N‐heterocycles through boron atom insertion is rarely reported in the literature. Here, we report a N‐heterocyclic editing reaction through the combination boron atom insertion and C−H borylation, accessing the fused‐BN‐heterocycles. The synthetic potential of this chemistry was demonstrated by substrate scope and late‐stage diversification of products. [ABSTRACT FROM AUTHOR]

Skeletal editing of N‐heterocycles has recently received considerable attention, and the introduction of boron atom into heterocycles often results in positive property changes. However, direct enlargement of N‐heterocycles through boron atom insertion is rarely reported in the literature. Here, we report a N‐heterocyclic editing reaction through the combination boron atom insertion and C−H borylation, accessing the fused‐BN‐heterocycles. The synthetic potential of this chemistry was demonstrated by substrate scope and late‐stage diversification of products. [ABSTRACT FROM AUTHOR]

Aliphatic amines containing N-heterocyclic fragments reacted with dialkyl [3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methyl] phosphonates to form 1,6-nucleophilic addition products. This approach was used to obtain α-aminophosphonates containing sterically hindered phenol and N-heterocyclic fragments in high yields. All the compounds were evaluated for their in vitro cytotoxicity with various cancer cell lines by MTT assay method. In the course of biological studies, it was found that the obtained compounds possess cytotoxic activity against some tumor cells. [ABSTRACT FROM AUTHOR]

Catalytic hydrogenation and oxidative dehydrogenation of N‐heterocycles to produce tetrahydroquinoline and quinoline derivatives are important reactions of particular importance in the agrochemical and pharmaceutical industries. Herein, we report earth‐abundant cobalt nanoparticles supported on hydroxyapatite (HAP) as an inexpensive and efficient catalyst for the hydrogenation and reverse oxidative dehydrogenation of N‐heterocycles. The optimal nanocatalyst exhibits excellent activity in both reactions for a wide range of substrates including (iso)quinolines, acridine, benzo[h]quinoline, quinoxaline and indole. Reactions proceed under relatively mild conditions without requiring any additives. [ABSTRACT FROM AUTHOR]

For more than a century, cutting-edge research in organic chemistry has been the discovery of novel, powerful synthetic procedures to create very significant N-heterocyclic scaffolds. Nitrogen-containing heterocyclic scaffolds owing to their extensive abundance in natural products and bioactive compounds has gathered a growing attention in both academical and industrial sectors in pursuit of development of highly efficient clinical targets and drug candidates. Given the significance of nitrogen-rich compounds in contemporary science, significant efforts have been conducted over the past few decades investigating effective techniques for synthesis of N-heterocycles. Due to its intrinsic flexibility and extensive range of applications, catalytic denitrogenative reaction employing transition metal has differentiated itself as a cornerstone among numerous initiatives. In the present article we have outlined the most recent breakthroughs in metal-catalyzed denitrogenative reactions, for proactive synthesis N-heterocycles. [ABSTRACT FROM AUTHOR]

Nitrogen‐centered radicals (NCRs) have been widely recognized as versatile synthetic intermediates for the construction of nitrogen containing molecules of high value. As such, there has been a long‐standing interest in the field of organic synthesis to develop novel nitrogen‐based radicals and explore their inherent reactivity. In this study, we present the generation of aromatic N‐heterocyclic radicals and their application in a novel and diverse functionalization of unactivated alkenes. Bench‐stable aromatic N‐heterocyclic pyridinium salts were employed as crucial NCR precursors, which enabled the efficient conversion of various unactivated alkenes into medicinally relevant alkylated N‐heterocyclic amines. This approach offers an unexplored retrosynthetic disconnection for the synthesis of related molecules that commonly possess therapeutic value. Furthermore, this platform can be extended to the synthesis of densely functionalized heterocyclic amines by utilizing disulfides and diethyl bromomalonate as radical quenchers. Mechanistic investigations indicate an energy transfer (EnT) pathway involving the formation of a transient aromatic N‐heterocyclic radical, radical addition to unactivated alkenes, and subsequent generation of the amination product through either hydrogen atom transfer (HAT) or radical addition processes. [ABSTRACT FROM AUTHOR]

Nitrogen‐centered radicals (NCRs) have been widely recognized as versatile synthetic intermediates for the construction of nitrogen containing molecules of high value. As such, there has been a long‐standing interest in the field of organic synthesis to develop novel nitrogen‐based radicals and explore their inherent reactivity. In this study, we present the generation of aromatic N‐heterocyclic radicals and their application in a novel and diverse functionalization of unactivated alkenes. Bench‐stable aromatic N‐heterocyclic pyridinium salts were employed as crucial NCR precursors, which enabled the efficient conversion of various unactivated alkenes into medicinally relevant alkylated N‐heterocyclic amines. This approach offers an unexplored retrosynthetic disconnection for the synthesis of related molecules that commonly possess therapeutic value. Furthermore, this platform can be extended to the synthesis of densely functionalized heterocyclic amines by utilizing disulfides and diethyl bromomalonate as radical quenchers. Mechanistic investigations indicate an energy transfer (EnT) pathway involving the formation of a transient aromatic N‐heterocyclic radical, radical addition to unactivated alkenes, and subsequent generation of the amination product through either hydrogen atom transfer (HAT) or radical addition processes. [ABSTRACT FROM AUTHOR]

This work describes the selective synthesis of a series of pyrido/benzo‐fused 1,4‐selenazines, through the reaction of bis(3‐amino‐2‐pyridyl) or bis(2‐aminophenyl) diselenides with different β‐dicarbonyl compounds. When molecular I2 was used as catalyst, a series of (Z)‐1‐(1H‐pyrido[2,3‐b][1,4]selenazin‐2(3H)‐ylidene)propan‐2‐ones were obtained. On the other hand, in the absence of catalyst, 1‐(2‐methyl‐1H‐pyrido[2,3‐b][1,4]selenazin‐3‐yl)ethan‐1‐ones could be prepared selectively. The structure of the prepared compounds was elucidated by NMR and HRMS analysis and confirmed by single crystal X‐ray diffraction. The versatility of the protocol was demonstrated not only by the access to a variety of 1,4‐selenazine derivatives, but also by the structural diversity in the 1,3‐dicarbonyl precursors, incorporating multifunctionalities in the synthesized heterocycles. [ABSTRACT FROM AUTHOR]

A series of eight new phosphonamidates containing sterically hindered phenolic and N-heterocyclic fragments was obtained and characterized. The synthesis is based on the reaction of O-alkyl-3,5-di-tert-butyl-4-hydroxybenzylchlorophosphonates with aliphatic amines. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: An unprecedented copper nitrate‐mediated bond cleavage of alkynes was developed for the modular synthesis of isoxazoles, where either C—S bond or C≡C triple bond was cleaved selectively. Substituents attached to the C≡C triple bonds could differentiate the chemical bonds cleavage and reaction pathways disparately. Various transformations of products illustrate promising applications of the given protocols. [ABSTRACT FROM AUTHOR]

A novel and efficient palladium‐catalyzed regioselective and stereodivergent ring‐closing reaction of aminoenynes with aldehydes and boronic acids or hydrosilane is developed. This three‐component reaction allows for the modular synthesis of a series of exocyclic 1,3‐dienes bearing 5‐ to 8‐membered saturated N‐heterocycles. The reactions utilize a simple Pd‐catalyst and work with broad range of aminoenynes, aldehydes and organometallic reagents under mild reaction conditions. The products represent useful intermediates for chemical synthesis due to the versatility of the conjugated diene. Preliminary mechanistic details of the method are also revealed. [ABSTRACT FROM AUTHOR]