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Synthetic electrochemistry may establish direct routes to a preparation of a plethora of organic substances, which are hardly accessible by conventional experimental techniques. Herein, we present an electrochemically‐driven method for an assembly of a broad range of rare heterocyclic mesoionic entities –1,2,3‐triazole 1‐imines. These nitrogen heterocycles were prepared through a transition‐metal‐ and exogenous oxidant‐free strategy using a C/Ni electrode pair. Over 30 examples of thus synthesized 1,2,3‐triazole 1‐imines illustrate selectivity and practical utility of this approach. Key solvent‐controlled reactivity patterns for the formation of the triazole imine scaffold were revealed indicating a modulation ability of the developed approach. These experimental findings were additionally justified based on cyclic voltammetry (CV) data and density functional theory (DFT) calculations. Moreover, according to differential scanning calorimetry (DSC) data, some of the prepared 1,2,3‐triazole 1‐imines correspond to the thermally stable species with an onset decomposition temperature up to 190 °C. [ABSTRACT FROM AUTHOR]

Numerous appropriately substituted pyridyl or phenyl groups serve as a particularly advantageous activation motif for the electrochemical oxidation of amines. Such groups enable a general, mild method for the electrochemical α‐functionalization of tertiary amines across numerous activating groups and amine scaffolds. Notably, the method accommodates an unprecedented range of nucleophile classes, allowing for the introduction of diverse functional groups to the readily prepared amine substrates. The utility of this method is then demonstrated through applications to unsymmetrical bisfunctionalization, site‐selective functionalization of N‐pyridyl amines vs. other activated amines, a formal synthesis of ivosidenib and the diversification of FDA‐approved drugs or natural product substrates. [ABSTRACT FROM AUTHOR]

The synthesis of chiral succinimides bearing all‐carbon quaternary stereocenters at the C3 position is important, but remains challenging. The present work demonstrates conjugate additions with catalysis by a chiral 1,10‐phenanthroline‐Pd complex (L1‐PdCl2) that exhibit complete regioselectivity with a high degree of enantioselectivity. These reactions afford chiral 3,3‐disubstituted succinimides having all‐carbon quaternary stereocenters with 40–99% ee. Importantly, chiral 3,3‐diaryl succinimides could also be obtained in 35–98% yields and 40–99% ee. Moreover, the present L1‐PdCl2‐catalyzed asymmetric conjugate addition could be performed on the gram scale and was also used to introduce such stereocenters into bioactive molecules. [ABSTRACT FROM AUTHOR]

Pyridines and quinolines substituted with sulfur‐containing functional groups are widely used as drugs, drug candidates, organic materials, N,S‐ligands and others. Traditional synthetic routes to produce these compounds are based on nucleophilic aromatic substitution reactions and transition metal‐catalyzed cross‐coupling reactions of (pseudo)halopyridines. While effective in many cases, both approaches are limited due to using forcing conditions and expensive, specifically designed catalytic systems. In the last decade, a number of innovative methods for the functionalization of the pyridine ring via the formation of a C−S bond have been developed. Most of these methods proceed through the direct or indirect C−H functionalization of unfunctionalized pyridines, thus avoiding the use of oftentimes not readily available halopyridines as the starting materials. Deoxygenative C−H functionalization of pyridine‐N‐oxides and deaminative transformation of aminopyridines have been also employed for the introduction of diverse organosulfur functionality into the pyridine ring. All these processes can be easily performed under mild conditions, typically affording value pyridines and quinolines in good to high yields. Usually being highly chemo‐ and regioselective, these methods allow the late‐stage functionalization of complex molecules including drugs and natural products. In this Review, we summarize the most recent synthetic methods for functionalization of pyridines and fused pyridines with sulfur‐containing functional groups reported mostly since 2018. For a better understanding of the processes, the mechanisms of the described reactions are briefly discussed. [ABSTRACT FROM AUTHOR]

We introduce a strategy for the one‐step synthesis of chiral diazabicycloalkanes that delivers the annulated ring system in a single reaction step. The method entails a direct aza‐Michael/aldol reaction of enals in conjunction with modified oxopropanamides and establishes the chiral center via iminium‐enamine tandem catalysis. For this purpose, we developed simple diphenylethylendiamine frameworks as dual activation organocatalyst, effectively engaging both the substrate and reagent, thus leading to yields of 31–86% and enantioselectivities in the range of 80–98%. The final product features not only the diazabicycloalkane moiety but includes also additional functionalities, such as aldehyde motives that can be modified in situ without loss of enantioselectivity, and an sp2‐bearing methyl group. Our approach accommodates a wide array of enals with high functional group tolerance. Additionally, we demonstrated the adjustability of enantioselectivity and yield by modulating the acid cocatalyst's quantity, thus offering multiple optimization possibilities. [ABSTRACT FROM AUTHOR]

Metal‐catalyzed asymmetric alkylation of indoles with α‐diazoesters is well‐known, however, the underlying mechanisms of this reaction, particularly the origin of stereoselectivity, remain uncertain. For the Pd catalysis, we address this cutting‐edge challenge from two complementary viewpoints – i) the molecular level regarding a single catalytically active Pd center; and ii) nano‐level Pd species investigating the factors favoring the appearance of the preferred catalytic centers. The formation of the active catalytic species was monitored by structural methods (NMR and ESI‐MS), and metal particles were characterized with electron microscopy (SEM, EDX). On the molecular level, chiral bipyridine‐N,N'‐dioxides proved to be competent chiral controllers. The kinetic and DFT computational data revealed a crucial role of water in the rate and selectivity determining steps and showed that the enantioselectivity of the process is controlled by the protodepalladation step. On the nano‐scale, the important effect of catalyst precursor on the overall reaction performance was shown. [ABSTRACT FROM AUTHOR]

A visible‐light‐mediated cycloaddition of azobenzenes and nonstabilized azomethine ylides has been developed to access 1,2,4‐triazolidines. With readily available organic dye rose bengal as a photocatalyst and alkyl tertiary amines as precursors for azomethine ylides, the reaction proceeded smoothly under visible light irradiation at room temperature, affording various 4‐alkyl‐1,2‐diaryl‐1,2,4‐triazolidines with yields of up to 96%. Preliminarily mechanistic studies suggest that the nonstabilized azomethine ylides are formed in situ through photoredox catalysis. [ABSTRACT FROM AUTHOR]

A photoredox‐promoted approach for the synthesis of [1,4]diazepino[1,7‐a]indol‐6(7H)‐ones starting from N‐indolyl phenylacrylamides and aroyl chlorides as radical source is reported. This method, that involves a cascade radical addition on C−C double bond followed by intramolecular cyclization at indole C2‐position, affords two diastereomeric indole‐fused 1,4‐diazepinones characterized by a N−C(aryl) axial chirality in yields ranging from 51 to 99%. [ABSTRACT FROM AUTHOR]

An acetic acid‐catalyzed [2+2+1+1] cycloaddition of 1,3,5‐triazinanes with methylene compounds was developed. This protocol provides an access to hexahydropyrimidines (HHPs) (25 examples) in 35–99% yields under mild conditions in 2 hours. The potential application of this method was demonstrated by gram‐scale synthesis. Preliminary mechanistic investigation was conducted to elucidate the possible mechanism. This work represents the yet unknown example of [2+2+1+1] cycloaddition reaction between 1,3,5‐triazinanes and active methylene compounds. [ABSTRACT FROM AUTHOR]

This report describes a general method for the one‐pot direct N‐acylation of N‐heterocycles using our previously developed 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. This system enables one‐pot N‐acylation reactions to provide bulky N‐acyl heterocycles starting from a wide variety of less nucleophilic N‐heterocycles and sterically hindered α‐fully substituted carboxylic acids in high yields. Moreover, this one‐pot method does not involve pre‐activation of substrates. The protocol has been successfully extended to one‐pot N‐acylation of 7‐azaindoles. [ABSTRACT FROM AUTHOR]

Carbolines are a prominent class of tricyclic alkaloids omnipresent in natural products and bioactive compounds. Four different carboline regioisomers are known (α‐, β‐, γ‐, and δ‐carbolines), which can be classified according to the nitrogen atom position inside the pyridine ring. As an emerging structural motif in drug discovery, a multitude of synthetic methods have been established for the construction of carboline frameworks, which in general requires customized approaches for the assembly of each regioisomer. Distinguishingly, their frameworks are also accessible from unified approaches, which are capable of generating multiple regioisomers, thus suitable for introducing diversity in isomeric carbolines. In this review, the construction of isomeric carbolines based on unified synthetic approaches is summarized. [ABSTRACT FROM AUTHOR]

2‐Pyrazolines are important five‐membered heterocycles, containing two adjacent nitrogen atoms. They can incorporate various functional groups and possess unique biological properties. Moreover, they have been used as useful building blocks. In recent years, the field of 2‐pyrazoline synthesis has experienced enormous progress. Novel strategies have been developed, and many studies reporting improvements or adaptations of existing protocols have been published, giving access to new functionalizations, unexplored structures, and/or enantioselective synthesis. This review summarizes the progress made in synthetic methodologies during the period from 2012 to 2022. The functionalization challenges and capabilities, scopes and limitations of the reactions, substitution patterns, and mechanisms of the reactions, where appropriate, will be discussed. [ABSTRACT FROM AUTHOR]

The catalyst‐controlled diversity‐oriented synthesis of spirohydroquinoline‐indandiones and 3‐methylenehydroquinoline‐indandiones from ortho‐sulfonamidophenyl‐substituted para‐quinone methides and allylidene‐indandiones is reported. The strategies utilized an organobase such as DMAP or TMG to control the reaction pathway chemoselectively, furnishing the corresponding products in 40–99% yields with excellent diastereoselectivities. The mechanistic studies revealed that spirohydroquinoline‐indandione was the kinetic product to afford 3‐methylenehydroquinoline‐indandione in the presence of TMG, which probably involved an unusual base‐initiated 1,3‐nitrogen rearrangement process. [ABSTRACT FROM AUTHOR]

A method of synthesizing o‐bis(3‐indolyl)arenes was developed by reacting indoles with 7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one and derivatives thereof having no aromatic ring. All 23 unknown o‐bis(3‐indolyl)arenes could be obtained using this method. Palladium catalysis is useful for enlarging the π‐conjugated area of o‐bis(3‐indolyl)arenes, delivering aryl‐, alkynyl‐, and alkenyl‐unit‐installed o‐bis(3‐indolyl)arenes, and benzo[c]indolo[2,3‐a]carbazoles, the derivatization to which is effective for raising fluorescence quantum yield. A possible reaction mechanism is proposed based on several mechanistic studies. [ABSTRACT FROM AUTHOR]

The synthesis of 2‐aminopyrrolo[1,2‐b]pyridazines from 1,3‐diynamides and 1‐aminopyrroles via gold(I)‐catalyzed chemoselective hydroamination/hydroarylation cascade was described. 26 examples were conducted to explore the scope of the substrates. A plausible reaction mechanism was also proposed. In addition, the fluorescence properties both in solutions and in the solid states of the resulting products were investigated. [ABSTRACT FROM AUTHOR]

A visible‐light photoredox functionalization of 3,4‐dihydro‐quinoxalin‐2‐ones with pyrazolones using an inexpensive organophotoredox catalyst is described. The reaction uses 9,10‐phenanthrenedione as photocatalyst, a very simple and cheap photocatalyst, a HP single Blue LED (455 nm) as visible‐light source and oxygen from air as terminal oxidant, obtaining the corresponding acetylated pyrazoles with good yields. The reaction can be extended to other nitrogen heterocycles such as 5‐aminopyrazoles with good results. [ABSTRACT FROM AUTHOR]

The combination of organolithium chemistry with gold catalysis has enabled the development of a synthetic strategy for accessing polysubstituted indoles and carbazoles from readily available starting materials. This method is based on a "back‐to‐front" approach from ketopyrroles, generated by intramolecular carbolithiation of N,N‐bis‐(2‐lithioallyl)amines that evolve into 3,4‐bis(lithiomethyl)dihydropyrrole intermediates capable of reacting with carboxylic esters and Weinreb amides. These ketopyrroles have demonstrated to be excellent precursors of mono or bis(alkynols)pyrroles that, under gold‐catalysis, experience a benzannulation reaction providing access to regioselectively substituted indoles or carbazoles. [ABSTRACT FROM AUTHOR]

Our recently developed gold‐catalyzed synthesis of indolo[1,2‐a]quinolines was successfully expanded towards bidirectional approaches, enabling access to two heptacyclic structural motifs. In the case of benzobispyrido[1,2‐a]indoles, previously inaccessible modifications of the only known representative were made possible. In addition, the synthesis of a new class of nitrogen‐containing heptacycles – namely benzobispyrrolo[1,2‐a]quinolines – was achieved by applying alkynylated benzodipyrrole derivatives as starting materials. All new compounds alongside with their corresponding precursors were fully characterized and their properties were investigated by X‐ray crystallography, photophysical measurements and computational methods. The study revealed important structure‐effect relationships between the solid‐state structures and the observed photophysical properties, e. g. aggregation‐induced emission and solid‐state fluorescence. [ABSTRACT FROM AUTHOR]

Saturated N‐heterocycles are prominent motifs found in various natural products and pharmaceuticals. Despite the increasing interest in this class of compounds, the synthesis of saturated bicyclic azacycles requires tedious multi‐step syntheses. Herein, we present a one‐pot protocol for the synthesis of octahydroindoles, decahydroquinolines, and octahydroindolizines through a cascade reaction. [ABSTRACT FROM AUTHOR]

This study reports the invention of di‐ or trifunctionalization of readily available pyridines (including all the pyridine substrates utilized in this paper, such as 3‐cyanopyridine and 3‐chloropyridine) through dearomative functionalization‐oxidative rearomatization under transition‐metal‐ and reductant‐free conditions. Although a two‐step operation is required, the crude product of the first step could be used in the next step directly. Typically, 3‐π‐EWG pyridines undergo difunctionalization, whereas 3‐σ‐EWG pyridines participate in trifunctionalization, affording multisubstituted piperidines. Computational studies provide detailed insights for their distinct reactivity in the title reaction. [ABSTRACT FROM AUTHOR]

Acylation of nitroalkylmalonates was found to yield substituted isoxazoline derivatives. This redox‐neutral transformation has a wide substrate scope and produces target products with yields up to 92%. Various substituents (aryl, alkyl, and ester) at the C3 and C4 positions of the resulting isoxazolines were also tolerated. A quick assembly of the isoxazoline ring starting from nitroalkenes and malonates was successfully developed. Control experiments showed that the intramolecular ring closure is the most likely key mechanistic step. Subsequent transformations into pyrrolidine and furane derivatives demonstrated the synthetic utility of the obtained products. [ABSTRACT FROM AUTHOR]

We report a procedure for the multigram synthesis of 4‐(dimethylamino)pyridinium azide, a stable, non‐explosive, low‐hygroscopic source of azide ion soluble in both protic and aprotic organic solvents. In protic ionic liquid media this reagent was shown to serve as a safer equivalent of toxic and unstable hydrazoic acid. The synthetic utility of this system was demonstrated using donor‐acceptor cyclopropane ring opening as a model process. General procedures furnishing a variety of dialkyl (2‐azido‐2‐arylethyl)malonates or 4‐azido‐4‐arylbutyrates, depending on the protic ionic liquid applied, were elaborated. The conversion times for studied donor‐acceptor cyclopropanes were established providing the relative reactivity sequence. The application of 4‐(dimethylamino)pyridinium azide for a conventional nucleophilic substitution, oxirane ring opening, (3+2)‐cycloaddition to (thio)cyano group as well as their combinations realized as telescopic synthesis was also demonstrated. [ABSTRACT FROM AUTHOR]

A selective Pd‐catalyzed C(3)−H cis‐functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono‐ and cis‐selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)−H functionalization reactions, which is facilitated by a DoE optimization. A one‐pot C−H functionalization‐epimerization procedure provides the trans‐3,4‐disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall, fragment compounds suitable for screening are generated in 3–4 steps from readily‐available heterocyclic carboxylic acids. [ABSTRACT FROM AUTHOR]

Disclosed herein is a photoinduced selective hydroamination of ynamides with nitrogen heteroaromatic nucleophiles. By using an organocatalytic photoredox system, a direct method to construct a diverse of (Z)‐α‐azole enamides from ynamides and pyrazoles, as well as triazoles, benzotriazoles, indazoles, and tetrazoles, is developed, thus providing a photocatalytically synthetic route to heterocyclic motifs common in medicinal agents. Based on the mechanistic studies, the hydroamination is postulated to operate via a mechanism in which the single‐electron oxidation of ynamide and the intermediacy of an alkyne radical cation, is responsible for the observed reactivity. [ABSTRACT FROM AUTHOR]

We report the method for synthesis of indole‐ and pyrrole‐fused seven‐membered nitrogen heterocycles by means of acid‐base switchable cyclization reactions. The reactions involved cleavage of amide C−N bonds, chemoselective N‐1 or C‐3 acylation, and 1,4‐Michael addition. This method could be used to construct two different kinds of seven‐membered rings in one step from the same starting material without the need for a transition‐metal catalyst. [ABSTRACT FROM AUTHOR]

Gold‐(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza‐spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out to demonstrate the robustness of the reaction. An intramolecular Mizoroki‐Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK1. [ABSTRACT FROM AUTHOR]

Propargylic glycols, 2‐alkynyl‐1‐(indol‐3‐yl)‐1,2‐diols, react with thiols undergoing a complex but selective gold‐catalyzed transformation that gives rise to α‐indol‐3‐yl α‐((Z)‐2‐thioalkenyl) ketones. The sequence is triggered by the regioselective thiolation of indolyl diols followed by an attack of the sulfur instead of the indole over the activated alkyne. The final compounds are obtained in remarkably high yields and arise from simple starting materials such as indolyl acyloins, ethynyl magnesium bromide and thiols. [ABSTRACT FROM AUTHOR]

Herein we report a site-selective and thiol-free thiofunctionalization of electron-rich heteroarenes. After a selective ortho-magnesiation, the use of S8 followed by an electrophile allows direct access to S-alkyl or -aryl derivatives. In situ oxidation provides the corresponding sulfoxide and sulfone derivatives. Applying this protocol, Cerlapirdine was prepared in 4 steps with 28% overall yield. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed one‐pot cascade cyclization of 2‐(1‐(acetyloxy)propargyl)benzaldehydes with o‐phenylenediamines for an access to substituted isoindolo[2,1‐a]quinoxalines has been developed. The reaction features readily available starting materials, simple operational procedure, and broad substrate scopes. Under optimal conditions, various isoindolo[2,1‐a]quinoxalines were afforded in 41–88% yields. [ABSTRACT FROM AUTHOR]

The review summarizes recent advances in the synthesis of C2‐halogenated nitrogen heterocycles via nucleophilic halogenation of corresponding N‐oxides as well as application of this methodology in the synthesis of pharmaceuticals. Both scientific and patent literature is reviewed mostly over the period of the last ten years. The review contains a practical guide (typical procedures and infographic based on extensive literature analysis), which can help practitioners in choosing optimal reagents/conditions for nucleophilic halogenation of N‐heterocycles of different types. The bibliography contains 199 references. [ABSTRACT FROM AUTHOR]

Indole is one of the most important heterocycles in organic synthesis, natural products, and drug discovery. Recently, tremendous advances in the selective functionalization of indoles have been reported. Although the most important advances have been powered by transition metal catalysis, exceedingly useful methods in the absence of transition metals have also been reported. In this review, we provide an overview of functionalization reactions of indoles that have been published in the last years with a focus on the most recent advances, aims, and future trends. The review is organized by the positional selectivity and type of methods used for functionalization. In particular, we discuss major advances in transition‐metal‐catalyzed C−H functionalization at the classical C2/C3 positions, transition‐metal‐catalyzed C−H functionalization at the remote C4/C7 positions, transition‐metal‐catalyzed cross‐coupling, and transition‐metal‐free functionalization. [ABSTRACT FROM AUTHOR]

In this review, the pivotal achievements and recent advances in catalytic asymmetric aza‐DAR reported up to 2020 are retrospectively considered and their potency for enantioselective synthesis of useful chiral piperidine, quinoline, pyridazine, oxazine and oxadiazine derivatives and fused compounds of higher molecular complexity bearing these pharmacology‐relevant heterocyclic scaffolds is demonstrated. The reported data are systematized according both to key electron transfer modes (normal or invers electron demand reactions) and to main types of attainable heterocyclic products. Of significant attention are an analysis of activation strategies (complexation, enamine or enolate formation, H‐bonding, etc.) applicable to reactions with particular types of dienes and dienophiles and identification of plausible reaction pathways (either concerted or stepwise) over stereoselective cyclization processes. The review contains 310 references and 122 synthetic schemes. [ABSTRACT FROM AUTHOR]

The Lewis (or Brønsted) acid‐catalyzed reaction of 2‐aryl‐N‐sulfonyl aziridines with ferrocene and ruthenocene provided new amino‐functionalized metallocene derivatives arising from a regioselective ring opening of the aziridine. The functionalized metallocene derivatives available by this methodology are suitable precursors for the stereoselective synthesis of metallocene analogues of the relevant tetrahydroisoquinoline motif by a Pictet‐Spengler type reaction. These isoquinoline analogues are also accessible by a TfOH‐catalyzed three‐component reaction of 2‐aryl‐N‐sulfonyl aziridines, ferrocene (or ruthenocene) and formaldehyde. [ABSTRACT FROM AUTHOR]

While remarkable progress has recently been made for the direct C−H‐functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon‐based) and poor regioselectivity. In contrast, C2‐functionalized pyridines and quinolines can be easily synthesized by treating readily available N‐oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2‐functionalization of pyridine and quinoline N‐oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics. [ABSTRACT FROM AUTHOR]

N‐(Pyrid‐2‐yl)‐substituted azolium and pyridinium salts, precursors for hybrid NHC‐containing ligands, were obtained with excellent regioselectivity, employing a deoxygenative CH‐functionalization of pyridine‐N‐oxides with substituted imidazoles, thiazoles, and pyridine. Unlike the traditional SNAr‐based methods, this approach provides high yields for substrates bearing substituents of different electronic nature. The utility of azolium and pyridinium salts thus prepared was also highlighted by the synthesis of pyridyl‐substituted imidazolyl‐2‐thione, benzodiazepine as well as 2‐aminopyridines. [ABSTRACT FROM AUTHOR]

Nitrogen heterocycles are important structural subunits that occur widely in bioactive natural products, pharmaceuticals, agrochemicals, dyes, cosmetics, and functional materials. Considering the importance of these useful compounds in modern science, the synthesis of N‐heterocycles and their derivatives has always been a hot topic in organic synthesis. Recently, arenediazonium salts which can be easily prepared from inexpensive and abundantly available anilines, have been used as versatile nitrogen sources in the field of nitrogen heterocycle synthetic chemistry due to their ready availability, rich reactivity, and diverse transformations. The aim of the present review is to summarize the recent advances in the synthesis of nitrogen heterocycles using arenediazonium salts as nitrogen sources in the past ten years. Hopefully, it can provide practical guidance for the readers who are interested in utilizing arenediazonium salts as building blocks in organic synthesis. For simplicity and clarity, the organization of this review is based on the number of N atoms in the ring of nitrogen heterocycle. [ABSTRACT FROM AUTHOR]

We have developed one‐step protocols for the preparation of a large selection of α‐aminocyclopropyl ketones or benzo[d]imidazoles, by reacting 2‐substituted‐2‐hydroxycyclobutanones with aryl amines or o‐phenylenediamines, respectively. In most case the reactions proceed at room temperature and are catalyst‐free. The formation of benzo[d]imidazoles is rationalized in terms of an unusual ring‐closure/ring‐fission process followed by aromatization. [ABSTRACT FROM AUTHOR]

A concise and practical method for the metal‐free synthesis of 1,8‐naphthyridones is described using a two‐step approach involving regioselective amination of pyridine N‐oxides and acid‐mediated cyclization. This is the first synthesis of 1,8‐naphthyridones utilizing easily accessible pyridine N‐oxides as substrates. Compared to previous reports, this method benefits from simple operation, easy access to starting materials, and a wide substrate scope, providing a variety of novel 1,8‐naphthyridones. [ABSTRACT FROM AUTHOR]

Metallocene catalysis is widely used in transformations of unsaturated organic compounds, including the bulk industrial synthesis of polyolefins. Over the last few decades, the electronic and structural properties of their η5‐coordinated ligands have been modified by introducing electron‐donating, electron‐withdrawing, and sterically hindered substituents to obtain desirable catalytic properties for the metallocenes. An efficient way to design η5‐coordinated ligands is to exploit the annelation of heterocyclic fragments with a cyclopentadiene ring. In the present review, we summarize, systematize, and analyze synthetic approaches to heterocycle‐fused cyclopentadienes suitable for metallocene catalyst preparation. [ABSTRACT FROM AUTHOR]

A one pot, three‐step cascade reaction to provide functionalized proline derivatives was developed. The Michael addition reaction of N‐allylated proline and activated alkyne forms a zwitterionic intermediate that further undergoes cyclization and [2,3]‐rearrangement to provide Cα‐alkylated proline bicyclic derivatives. This transformation was highly stereoselective and the chirality of the N‐allylated prolines was completely transferred to the product via a C−N−C chirality transfer process. The developed reaction is operationally simple and does not require any reagents other than the substrates. [ABSTRACT FROM AUTHOR]

We present the instance of two aromatic double bonds and an imine double bond involved thermal 6π‐azaelectrocyclization and, on this basis, a one‐step synthesis of triazacoronenes (TACs) from triphenylene‐1,5,9‐triamines and aldehydes under nonacidic conditions. This method has several advantages such as simplicity, high yields, and extensive substrate scope. A plausible reaction mechanism has been proposed with several experimental supports. A typical derivative shows a unique dimer holding together via a π‐π interaction and six H‐bonds and a zigzag superstructure stabilized by three centered H‐bonds and Br ⋅⋅⋅ π interaction between the adjacent dimers. [ABSTRACT FROM AUTHOR]

Tandem catalysis, the use of a single catalyst to promote two or more mechanistically distinct cycles in one pot to assemble complex organic molecules, is an attractive target. In this paper, we report a reductant‐triggered tandem palladium catalysis process that rapidly assembles 3,4‐fused tricyclic indoles from three readily available starting materials. This tandem process involves a Pd0‐catalyzed in situ coupling/cyclization/Michael addition reaction to install simultaneously two functional groups at the C4 and the C3 positions of indoles. This is followed by a Pd0‐catalyzed intramolecular cyclization which builds a seven‐membered C4, C3‐bridge. Sodium formate is used to trigger the necessary switching between the palladium catalysed reactions. [ABSTRACT FROM AUTHOR]

A selective synthesis of 5,6‐disubstituted and 5‐substituted indazolo[2,3‐a]quinolines through a Rh(III)‐catalyzed oxidant‐free annulation of 2‐aryl‐2H‐indazoles with α‐diazo carbonyl compounds is reported. With 2‐aryl‐2H‐indazoles as the substrates, α‐diazo carbonyl compounds could act as a C2 synthon to afford 5,6‐disubstituted indazolo[2,3‐a]quinolines via a Rh(III)‐catalyzed [4+2] annulation. On the other hand, when 2‐aryl‐3‐formyl‐2H‐indazoles were used as the substrates, α‐diazo carbonyl compounds switched to act as a C1 synthon to undergo a more complicated [5+1] annulation process to furnish 5‐substituted indazolo[2,3‐a]quinolines. [ABSTRACT FROM AUTHOR]

A silver(I) triflate‐catalyzed protocol for the post‐Ugi synthesis of tetracyclic spiroindolines has been developed. The protocol worked best for indole‐3‐carbaldehyde‐derived Ugi adducts obtained using anilines and 3‐aryl propiolic acids. Thus, it is complementary to the previous cationic gold‐catalyzed procedure that was developed for analogues Ugi substrates derived from aliphatic amines and 3‐alkyl propiolic acids. Furthermore, we have demonstrated that under our new settings this domino Friedel‐Crafts ipso cyclization / imine trapping process could be efficiently combined with the preceding four‐component Ugi reaction into a two‐step one‐pot transformation. [ABSTRACT FROM AUTHOR]

A novel access to isoxazolines was developed using the [4+1]‐annulation of α‐keto‐stabilized sulfur ylides with N,N‐bis(siloxy)enamines derived from aliphatic nitro compounds. The resulting 5‐keto‐substituted isoxazolines were shown to be convenient precursors of polysubstituted 3‐hydroxypyrrolidines via the one‐pot catalytic N−O hydrogenolysis/intramolecular reductive amination sequence. Application of this approach to the formal synthesis of Merck's potent NK1 receptor antagonist was demonstrated. [ABSTRACT FROM AUTHOR]

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate‐driven synthesis of β‐enaminones and N‐aryl pyrroles from indolizines and nitrosoarenes; aryl‐substituted indolizines lead to β‐enaminones in a regio‐ and diastereoselective manner, whereas alkyl‐substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the β‐enaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work. [ABSTRACT FROM AUTHOR]

Heterocycles are generally biologically active compounds and are the main basic scaffolds in many natural and non‐natural moieties. Recently, silver‐catalyzed syntheses have undergone remarkable progress in the field of synthetic heterocyclic chemistry. This review summarizes the recent trends in the silver‐catalyzed synthesis of nitrogen‐containing heterocyclic compounds. [ABSTRACT FROM AUTHOR]

A protocol was developed for the synthesis of 3‐thioindoles in good‐to‐excellent yields involving sulfenylation between 2‐nitrocinnamaldehydes and various thiols using a well‐defined copper(I)‐phosphine complex catalyst. This unconventional divergent approach involves in situ generation of indoles via domino C−S/C−N bond formation initiated by sulfa‐Michael addition followed by intramolecular N‐heteroannulation. This protocol shows good chemoselectivity and broad substrate scope. To briefly demonstrate the value of this approach, 2‐benzoyl‐3‐sulfenylated indoles were prepared from commercially available 2‐nitrochalcones and thiols. [ABSTRACT FROM AUTHOR]

A catalytic nucleophilic addition reaction of 3‐hydroxybenzofuran‐2‐carboxylic acid derivatives to 2H‐azirines for the high‐yield synthesis of NH‐aziridines with a 3‐coumaranone substituent has been developed. The Ph3PAuNTf2‐catalyzed reaction is diastereoselective to give predominantly (RS,SR)‐isomer of aziridine in good yield. The Ni(hfacac)2‐catalyzed reaction affords aziridines in up to 98% yield and low or moderate diastereoselectivity, which in some cases is opposite to that observed for the gold(I)‐catalyzed reaction. The Ph3PAuNTf2 works well for sterically hindered azirines as well as benzofurans bearing electron‐withdrawing groups, whereas Ni(hfacac)2 is the catalyst of choice for the preparation of aziridines having diazoacetyl substituent. The latter compounds can serve as substrates for the synthesis of fused aziridines via Buchner ring expansion reaction. [ABSTRACT FROM AUTHOR]