Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• diastereoselectivity (up to 7:1). Keywords: alcohols; diastereoselectivity; nitrogen heterocycles; pyrazoles; vinylogous reaction; Introduction Vinylogy refers to the transmission of electronic effects through a conjugated π-system, enabling the extension of a functional group's nucleophilic or electrophilic

• biologically active compounds, particularly antibacterial and antifungal agents [13][14]. This class of functionalized nitrogen heterocycles is notable for its synthetic versatility, because it shows different nucleophilic positions, making regioselectivity a synthetic challenge. Numerous studies have reported

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• that benzofuran adduct 15c was previously reported by Dyker to be obtained in only 10% yield when 12 was reacted with 10 equivalents of unsubstituted benzofuran, in the presence of 5 mol % of Pd(OAc)2 at 100 °C for 3 days [52]. The compatibility of five-membered nitrogen heterocycles with our

• methodology was further examined with (1-methyl-1H-pyrazole-5-yl)boronic acid pinacol ester as the pyrazole ring is one of the most frequently occurring aromatic nitrogen heterocycles among the pharmaceuticals approved by the U.S. FDA between 2013 and 2023 according to a recently-reported analysis [53]. With

• %, Table 2, entry 4). Afterwards, we sought to examine the reactivity of six-membered aromatic nitrogen heterocycles. The reactions of (2-methoxypyridin-3-yl)boronic acid with the dihalonaphthalenes 12 and 14 afforded substituted azafluoranthenes 15f and 15g in 90 and 51% yields, respectively (Table 2

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• rearrangement to form C(sp2)–O bonds without the need of metal catalysts [82]. In 2023, this approach was expanded to synthesize complex functionalized aromatic ring diaryliodonium salts [83]. Various aromatic rings, including multisubstituted arenes, conjugated arenes, oxygen and nitrogen heterocycles 78 were

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• the reaction protonates the amino group, making the final cyclization less efficient. Finally, we have tried to extend the synthetic protocol to other benzo-fused N-heterocycles. We investigated the benzo-fused 7-membered nitrogen heterocycles, both for our previous experience in applying them in MCRs

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• thermostable components of functional organic materials. Keywords: molecular hybridization; nitric oxide; nitrogen heterocycles; 1,2,5-oxadiazoles; 1,2,3-triazin-4-one; Introduction Nitrogen heterocycles are a significant and broad class of organic substances included in the structure of various natural

• . 1,2,5-Oxadiazoles (furazans) and their N-oxides (furoxans) are important representatives of nitrogen heterocycles due to their wide applications in various fields of medicine, chemistry, and materials science [6][7]. For example, these heterocycles serve as valuable building blocks for the synthesis of

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• Javier Gomez-Ayuso Pablo Pertejo Tomas Hermosilla Israel Carreira-Barral Roberto Quesada Maria Garcia-Valverde Departamento de Química, Universidad de Burgos, Burgos 09001, Spain 10.3762/bjoc.20.154 Abstract Piperazines and diazepines are examples of nitrogen heterocycles present in many marketed

• strategies to easily generate multiple fused nitrogen heterocycles including benzodiazepinone and piperazinone cores. Keywords: arylglyoxals; deactivated amines; nitrogen heterocycles; Ugi reaction; Introduction Nitrogen heterocycles such as piperazines or diazepines represent important systems in the

• limited reactivity, modulated by their substitution [19]. Results and Discussion Synthesis of 3H-benzo[e][1,4]diazepin-5-ones As part of our continued interest in developing new and efficient strategies for synthesizing complex fused nitrogen heterocycles, we decided to evaluate the use of amine groups

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• ]triazol-4-yl)pyridines was observed. Keywords: aromatic nitro compounds; Boulton–Katritzky rearrangement; isoxazolo[4,5-b]pyridines; nucleophilic substitution; 1,2,3-triazoles; Introduction Nitrogen heterocycles represent a very important class of organic compounds that has found application in various

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• desired product, which proved to be unstable during purification (Scheme 4). Homopropargylic azides containing electron-rich nitrogen heterocycles could not be obtained. No product was observed by using vinylindole 1d probably due its high tendency to polymerize. Although a slight amount of

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• tetrachlorophthalimide (TCPhth) active esters towards C(sp3)–N cross-couplings with nitrogen heterocycles (Scheme 27). The catalytic reaction was proposed to begin by oxidative addition of RAE 104 to catalyst Bi-1, forming an in cage radical pair consisting of BiII species 130 and α-amino radical 107 (Scheme 27B

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• , MIC·CS2, and NHC·CS2 zwitterions displayed similar electronic properties and featured the same bite angle. Yet, their steric properties are liable to ample modifications by varying the exact nature of their cationic heterocycle and its substituents. Keywords: betaines; carbenes; ligand effects; nitrogen

• heterocycles; zwitterions; Introduction Following the seminal discovery from the group of Arduengo, who isolated and fully characterized 1,3-di(1-adamantyl)imidazol-2-ylidene in 1991 [1], stable divalent carbon species have evolved from fleeting intermediates to ubiquitous catalysts, ligands, and reagents in

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• molecules and CRBN ligands are being published (over 400K patents in the last 5 years according to SciFinder). Various nitrogen heterocycles were utilized as a heterocyclic moiety linked to a glutarimide core via a nitrogen atom. In addition to the phthalimide fragment, the most commonly studied ones are

• will be reported in the following works. Conclusion In summary, a new diazo reagent for the convenient incorporation of heterocyclic substituents at the alpha-position of glutarimide by Rh(II)-catalyzed insertion of carbene into the N–H bond of nitrogen heterocycles has been proposed. The method allows

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• the Lewis acid to realize the sp3 C–H-bond activation of nitrogen heterocycles to synthesize isoxazole derivatives. Results and Discussion At the outset of this study, we chose the reaction of 2-methylquinoline (2a) with phenylacetylene (1a) in the presence of AlCl3 (3 equiv) and sodium nitrite (10

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• reactions, and C–H functionalizations ([3] and references therein), leading to the synthesis of diverse nitrogen heterocycles of pharmaceutical relevance [4]. The traditional synthetic method for the preparation of N-arylsulfonylimines, similar to the preparation of N-arylimines, is based on the

• deliver N-arylsulfonylimines under mild reaction conditions is highly desirable. Previously, we reported a tandem oxidative intramolecular cyclization of N-aryl(benzyl)amines, having an internal nucleophile substituted at the ortho-position in the aniline ring, to nitrogen heterocycles using potassium

• nucleophilic addition and as a result the corresponding cyclized product is not formed. The synthesis of these nitrogen heterocycles signifies the innate ability of in situ-generated N-arylsulfonylimines in a variety of reactions with various ortho-substituted anilines without the need for pre-isolation or

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• -membered nitrogen-heterocycles [10]. Whereas an aza-Nazarov-type cyclization may be operative in some earlier examples [11][12][13][14][15], general interest in this area increased after the elegant studies of Würthwein and co-workers where they utilized the aza-Nazarov cyclization for the construction of

• ) group via the β-silicon stabilization effect [36][37][38] as supported by computational studies [35]. The desilylation of intermediate 9 with the chloride of another molecule of 8 would result in the formation of final aza-Nazarov product 7 along with TMSCl (Scheme 1d). Five-membered nitrogen

• -heterocycles [39][40][41][42][43][44][45] and specifically α-methylene-γ-lactams as a subset of this compound class, are popular targets in heterocyclic chemistry and drug discovery [46][47][48][49][50][51][52][53][54][55][56]. Against this background, we herein disclose a full account of our studies on the

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• fluorescent materials containing Lewis basic nitrogen heterocycles are more likely to provide the feasible band gap modulation. The essence of such phenomenon originates from Lewis acid–base coordination and adducts, which highly depends on the electron-accepting property of the Lewis acids. This

• hinder the coordination with a Lewis acid. For example, Bazan’s group investigated the analogous compounds 21 and 22 shown in Figure 13a, featuring the same nitrogen heterocycles but with different steric hindrances. Subsequently, the ability of their coordination with B(C6F5)3 and BBr3 was compared

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• ]. Moreover, the number and nature of various side units on the emitter framework can also affect the properties of TADF compounds [3]. Among the electron-donating units, 9,10-dihydroacridine, carbazole or phenoxazine derivatives often are used as D units, while the π-electron-deficient nitrogen heterocycles

• of aryl moieties into methylthio-substituted nitrogen heterocycles such as tCBz-mPYR are a Ni(0)-catalyzed cross-coupling reaction with Grignard reagents [34][36] or the Liebeskind–Srogl reaction employing arylboronic acids [37][38][39]. Taking into account a large assortment of arylboronic acids and

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• which realizes for the construction of medium-sized saturated nitrogen heterocycles [21]. Although the process enables the rapid construction of saturated nitrogen heterocycles from acyclic precursors, it requires homogeneous precious transition metal complexes as photocatalysts. On the other hand

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• correlates with the literature data [49]. In addition, there were some marginal differences between the bond lengths in the two 1,2-oxazole rings. Conclusion A series of novel 1,2-oxazole-4-carboxylate derivatives possessing Boc-protected 4-, 5- and 6-membered saturated nitrogen heterocycles were synthesized

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of natural product-like compound libraries. Keywords: [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines; Introduction An important design concept in current drug discovery includes structural modifications of naturally occurring

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• organocatalysts in asymmetric aza-MR. Keywords: asymmetric aza-Michael reaction; covalent bonding catalysis; nitrogen heterocycles; non-covalent bonding catalysis; organocatalysis; Introduction The Michael reaction though discovered about 135 years ago [1][2] continues to attract attention of the chemists owing

• -MRs, each highlighting a certain aspect of the reaction. While Sánchez-Roselló et al. [18] classified these reactions on the basis of the nature of the substrates, Nayak et al. [19] and Bhanja et al. [20] focused on the stereoselective synthesis of nitrogen heterocycles via Michael cascade reactions

• . Recently, Vinogradov et al. [21] reviewed the synthesis of pharmacology-relevant nitrogen heterocycles via stereoselective aza-MRs. On the other hand, Enders et al. [22], Wang et al. [23] as well as Krishna et al. [24] highlighted the scope and catalytic performances of some organocatalysts in asymmetric

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• high levels of selectivity, reactivity, and functional group tolerance, providing a large number of complex nitrogen heterocycles like azaindolines, pyrrolo-quinolines and -quinolones in excellent yields. Amongst the synthesized scaffolds, especially azaindolines are known to be present in M4

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• ] systematically surveyed simple nitrogen heterocycles and found that the 3-pyridazinyl nucleobase formed significantly more stable triplets with C–G than other heterocycles, including P. Several groups have explored extended PNA nucleobases for recognition of C–G base pairs [121][122]. Chen and co-workers

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• irradiation with sunlight, which facilitates the transport of electrons through the system (Scheme 4). Certain nitrogen heterocycles can be inserted into the substituent chain as an acceptor structural unit (Scheme 5). For example, an OSC based on a symmetrically substituted isoindigo derivative 4 containing

• best efficiency. Monoisoindigos with preferred 6,6'-substitution. Possibility of aromatic–quinoid structural transition. Isoindigo structures with incorporated acceptor nitrogen heterocycles. Monoisoindigos bearing pyrenyl substituents. p-Alkoxyphenylene-embedded thienylisoindigo with different

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• ; electron transfer; γ-lactams; tandem reactions; Introduction Nitrogen-containing heterocycles are widely distributed in biologically active compounds [1][2][3][4]. Saturated nitrogen heterocycles such as pyrrolidines [5][6][7][8][9], piperidines, pyrrolizidines or indolizidines [10][11][12][13][14][15][16

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• electrophilic metal-bound iminocarbenes form. These iminocarbenes undergo a variety of intriguing reactions, such as a cycloaddition and a C–H functionalization, among others, leading mostly to nitrogen heterocycles [8][9][10]. Using this chemistry, a variety of pyrroles have been prepared starting from N

• -sulfonyl-1,2,3-triazoles (Scheme 1) [11][12][13][14][15][16][17]. We have recently reported that N-perfluoroalkyl-1,2,3-triazoles [18] undergo rhodium-catalyzed transannulation reactions leading to various nitrogen heterocycles, such as imidazoles, pyrrolones, imidazolones, oxazoles, azepines [19][20][21

• trifluorometylated compounds is essential for future progress in areas that eventually improve the quality of life. In this context, N-trifluoromethylated compounds (amines, amides and nitrogen heterocycles) are a relatively underexplored group of molecules with a high potential in medicinal chemistry [29][30