Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• useful strategic transformations for the construction of carbocyclic and heterocyclic cyclopentanes. Six-membered carbocycles are convenient starting compounds for the synthesis of cyclopentanoids due to their widespread occurrence in nature and their synthetic availability. Undoubtedly, the development

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• context of these strategies, it would be judicious to consider cycloaddition reactions of the [3 + 2] type, a field in which Smith and Huisgen are recognized as pioneers [24][25]. In the field of heterocyclic chemistry, the [3 + 2] type of cycloaddition reaction is a widely employed method for the

• formation of the five-membered isoxazolidine ring motif, which displays a range of biologically active properties [26][27][28][29][30]. It is notable that the fused pyrrolo-isoxazolidines represent a particularly versatile class of heterocyclic compounds and intermediates, which have been demonstrated to

• -based nitrone with some maleimides via a mechanochemical route in a solvent-free medium [67][68]. The development of environmentally friendly green methodologies for the preparation of heterocyclic compounds via such cycloaddition reactions is a significant and ongoing research area that should not be

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• ], ion pairs [15], N-heterocyclic carbene (NHC) catalysts [16][17][18], or thiols [19][20][21] are not covered here but can also be effective for achieving high levels of enantioselectivity in radical reactions. Lewis acid-catalyzed radical reactions In the context of enantioselective radical reactions

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• heterocyclic scaffolds, which established a versatile platform for synthesizing structurally diverse indoline frameworks. Ligand-controlled cyclization of 1,n-enynes The core function of catalyst ligands lies in their ability to precisely modulate catalyst performance through electronic and steric effects. The

• cyclization, yielding a six-membered ring product 72 (Scheme 15, path b). This observed selectivity arose from differential stabilization of transition states by ligands, thereby enabling the Au(I)-catalyzed cyclization to directly access bioactive heterocyclic frameworks commonly encountered in natural

• intermediate 76 to drive hydrolysis. This methodology tolerates structurally diverse 1,7-enyne esters and generates defined cis-1,2,3,6-tetrahydropyridine scaffolds, which serve as synthetic intermediates for complex natural products and pharmacologically relevant heterocyclic frameworks. In 2016, Jiang group

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• piperazinone ring. Keywords: benzodiazepine; click reaction; multicomponent reaction; one-pot; piperazinone; polycyclic; triazole; tetrazole; Ugi–azide reaction; Introduction Triazole, tetrazole, and benzodiazepine are privileged heterocyclic rings commonly found in drug molecules and functional materials [1

• heterocyclic scaffolds to obtain biologically interesting compounds (Scheme 1) [35][36][37][38][39][40][41]. The development of methods for the synthesis of triazole, tetrazole, piperazinone, and 1,4-benzodiazepine motifs are attractive from both synthetic and medicinal chemistry considerations [42][43][44][45

• , the Ugi–azide adducts could undergo lactamization and lead to the formation of highly condensed 1,4-benzodiazepines 8 fused with triazole, tetrazole, and piperazinone rings. This is a new example of combining MCR and post-condensation modification as a one-pot synthesis to access novel heterocyclic

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• heterocyclic scaffolds are widely used in the treatment of various diseases, making them a common focus of research [1]. A substantial part of these compounds incorporate five- or six-membered nitrogen heterocycles. The indole and quinazoline cores represent two pharmacologically significant heterocyclic

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• formation of heterocyclic systems in a minimal number of steps and offer several ways to vary substituents and they are widely used in drug discovery and development, as well as in diversity-oriented synthesis [1][2][3][4]. In addition, the application of condition-based divergence strategy [5] and the

• -1,2,4-triazoles, is important because the formation of different chemotypes of final heterocyclic compounds are possible depending on the structure of the reagents, the solvents and the catalysts, and type of activation methods [7][8][9]. MCRs of aminotriazoles, methylene-active compounds, and

• NMR spectra of heterocyclic acids 5a–c exhibited a broad singlet of proton of the carboxyl group at 11.88–14.02 ppm, a singlet of proton of the hydroxy group at 9.41–9.86 ppm, a singlet of proton of the pyrimidine NH group at 7.72–7.91 ppm, a singlet of proton of the triazolylamine NH group at 7.44

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• possibility of synthesizing various heterocyclic systems such as quinazolines [25], diazepinones [25][26], quinoxalinones [27], diazocinones [28], and imidazolines [29] due to the exceptional reactivity of the azido group. However, the use of azido amines in the Ugi reaction together with oxoacids, which have

• nitrogen-containing heterocyclic compounds using various modifications of this sequence [32][33][34][35][36]. Among others, Yan et al. [31] described a facile way to quinoxalinone derivatives using an Ugi/Staudinger/aza-Wittig tandem combination with pyruvic acid or phenylglyoxylic acid. Quinoxalinones are

• regarded as privileged heterocyclic moieties in the development of new pharmacologically active organic compounds (Figure 1) [37]. These structures are of great interest to chemists because of their broad spectrum of potential biological effects, including anticancer [38], antibacterial [39] and anti-HIV

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• 22, 14195 Berlin, Germany School of Natural and Environmental Sciences, Newcastle University, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK 10.3762/bjoc.21.153 Abstract Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed

• ; carbonyls; NHCs; photochemistry; reduction; Introduction The introduction and exploration of N-heterocyclic carbenes (NHCs) ranks among the most important developments in chemistry research of the last 30 years [1][2][3]. In addition to their numerous valuable roles as ligands, including for important

• applications, are underway in our laboratory. (a) Combining N-heterocyclic carbene (NHC) organocatalysis with photoredox catalysis for radical–radical coupling reactions. (b) This work: light-mediated reduction of acylimidazolium species 1 with the tertiary amine DIPEA or the simple silane HSiEt3. Initial test

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• electrochemical cyclization process. In contrast, more complex and extended heterocyclic electronrich π-systems such as compound 2j was obtained in 35% yield only, presumably as a result of electronic factors affecting the efficiency of the initial radical formation [47]. To further extend the scope of this

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• , Corminboeuf, Samanta, and König [6][31][32][33][34][35]. Although they do not possess an azo bond, heterocyclic imines are worth mentioning in this chapter due to their similarity to the azo-compounds and their straightforward synthesis. Substitution of the azo bond with an imine bond gives rise to

• heterocyclic imines [36][37][38]. The Z-isomers of the unsubstituted derivatives adapt different conformations: T-shaped for the N-phenyl and twisted for the N-pyrazoles. The half-lives follow the same trends already discussed beforehand. In contrast with the azopyrazoles, mono- and di-ortho-amination of the

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• in active pharmaceutical ingredients, therapeutic agents, and agrochemical formulations [1][2][3][4][5][6][7][8][9]. Around 60% of recently FDA-approved drugs contain heterocyclic compounds, with quinoline recognized as a key structural motif due to its significant anticancer, antifungal

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• -membered heterocyclic ring are of particular interest, since they exhibit a wide range of pharmacological activity (Scheme 1) [6][7][8][9][10][11]. The most straightforward and powerful methods of such substance’s syntheses are based on cycloaddition reactions [12][13][14][15]. Previously, we and other

• were formed, and the transformation rate was extremely low. This outcome may be attributed to the electron-acceptor properties of the oxygen atom, which likely disrupt the cycloaddition process. NMR analysis confirmed that each heterocyclic ring formed products exclusively as a single diastereomer

• transformations. For example, compound 7e underwent both sulfone formation and S/O atoms exchange in the heterocyclic core. For derivatives 6 and 8, any oxidation conditions resulted in even more complex product mixtures (presumably due to the additional sulfur atom in the second ring), whose structures could not

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• unique ability of these compounds to undergo selective opening of the three-membered ring at either of the two nitrogen–carbon bonds under certain conditions and to be incorporated into the target molecule as a N‒C‒C synthon is successfully used to obtain a variety of heterocyclic and acyclic nitrogen

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• bioactive fragments into a single molecule through a spacer. An alternative strategy of combining heterocyclic pharmacophores is to incorporate them into a spiro-jointed structure that lacks any intermediate link between the active parts [17]. Despite the fact that these strategies share numerous

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

• -mediated reaction for the synthesis of enaminones from 3-bromochromones (Scheme 1D). Initially, a Ni(II)-catalyzed hydroamination protocol affords the intermediate 2-amino-3-bromochromanones, which upon photocatalytic dehalogenation and subsequent opening of the heterocyclic ring provide the corresponding

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• of non-concerted, step wise cycloadditions leading to mixtures of five- and seven-membered heterocyclic products (cycloadducts), and respective zwitterionic intermediates were postulated to explain the unexpected reaction pathway [11]. Due to the practically equal electronegativity of carbon and

• terminal S‒CH2 position, leading to the formation of the sulfonium cation 11 and the delocalized heterocyclic anion 12 (Scheme 6). In the next step, competitive addition of both intermediate species yields either thioaminals 9 or dithioacetals 10. However, a slow isomerization of the thermodynamically less

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• synthesis of various benzoxazole derivatives, demonstrating its versatility and practical applicability. Keywords: aerobic oxidation; copper; grafted silica; heterogeneous catalysis; microwave; Introduction 2-Aminoazoles are nitrogenous heterocyclic compounds of high relevance due to their biological and

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• data, compound 3aa crystallizes in the centrosymmetric spatial group of the monoclinic system. The molecule has a tweezer-like conformation due to π–π interactions between the electron-donating tolyl and the electron-acceptor fragment NC‒C=C‒S. The heterocyclic fragment in the molecule is non-planar

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• imidazole-based N-heterocyclic carbene (NHC)–CuCl complexes [40]. However, their synthesis is often tainted by the use of toxic reagents and solvents. In addition, when o-phenylenediamine reacts with ketones, the common catalytic methods yield benzodiazepine products [41]. In our case the reaction of o

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• chemistry; natural products; oxetane; reactivity; synthesis; Introduction Oxetanes are 4-membered heterocyclic compounds containing one oxygen atom whose discovery dates back to the 1870s when the first synthesis of the parent, unsubstituted oxetane was reported by Reboul [1]. Over the next 100 years, it

• enantioselectivities. In 2018, Scheidt and colleagues disclosed the first N-heterocyclic carbene (NHC)-catalysed [2 + 2] annulation between trifluoromethyl ketones and γ-substituted allenoates (Scheme 25a) [68]. The resulting 2-alkylideneoxetane products 95 were generally obtained in >90% yields and good

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• for constructing quaternary carbon centers in oxindoles via an N-heterocyclic carbene (NHC)-catalyzed intermolecular Heck-type alkyl radical addition and annulation reaction (Scheme 47) [28]. The reaction proceeds through a redox-neutral mechanism, where the NHC catalyst serves a dual role as both a

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• modifications of MCRs could generate novel and complex molecular scaffolds [1][2][3][4][5][6][7][8]. Some MCR adducts generated from Ugi, Passerini, Gewald, Biginelli, and Groebke–Blackburn–Bienaymé (GBB) reactions have been modified to form chemically diverse heterocyclic scaffolds with potential biological

• reaction followed by the cleavage of the alkyl group to give intermediate II as a free amine. Annulation of II with CDI gave product B which is an HIV reverse transcriptase inhibitor (Scheme 1B) [17]. We have reported a three-component [3 + 2] cycloaddition followed by IMDA reaction for making heterocyclic

• group on the imidazopyridine moiety have direct electronic impact on the IMDA reaction. This integrated reaction process provided a new avenue for the preparation of heterocyclic scaffolds with potential biological activity. Experimental General procedure for the synthesis of intermediates 4 and 6 The