Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• concerns and improved reaction control can be addressed, paving the way for more efficient and sustainable synthetic methodologies. Keywords: cascade reactions; formaldehyde surrogates; green chemistry; heterocycles; multicomponent reactions; Introduction Organic chemistry is a mature discipline that has

• the MCR product is possible thus increasing the versatility of these reactions in terms of structural diversity and molecular complexity. In this context, a wide variety of heterocycles and macrocycles as important biological scaffolds have been synthesized [6]. One of the most important components

• the cyclization process producing various highly diverse nitrogen-containing heterocycles, which are valuable scaffolds in medicinal chemistry [46]. Synthesis of non-aromatic heterocycles As stated above, DMSO can also hydrolytically decompose to formaldehyde. There are many examples of reactions in

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• ][9]. Wherein, the wide variety of easily available starting butenolides and amines allows one to create a huge array of practically useful products. At the same time, the application of hydrazine derivatives expands the range of formed heterocycles. So, along with the aforementioned N-substituted

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 electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• novel compound DPQ1. Keywords: deazapurines; heterocycles; pyrrolopyrimidines; queuosine; riboswitches; ribozymes; RNA alkylation; RNA labelling; Introduction Pre-queuosine 1 (preQ1) is a biosynthetic precursor of the hypermodified nucleoside queuosine (Q) that is found in the wobble position of

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• and step-economy, making them promising for future commercial applications. Partly hydrogenated isoindoles and their derivatives exhibit broad biological activities and are considered privileged motifs in medicinal chemistry [20][21]. These compounds, when condensed with aromatics or heterocycles

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• ], offering enhanced properties and efficacy [28][30][33][34][35]. Therefore, the advancement of simple, efficient methodologies for synthesizing o-carborane-fused heterocycles is critically needed. However, the limited number of synthetic strategies for carborane functionalization [36] continues to constrain

• , whereas the boron cage is aromatic, the heterocyclic ring is clearly non-aromatic, with MCI that amount to 0.002, 0.000 and 0.003 a.u., respectively (Figure 4). At difference, based on NICS, these heterocycles should be considered aromatic (−8.5, −7.1, and −8.3 ppm, respectively). However, we have

• neighboring cycles exhibit high or very high NICS values. For a more reliable evaluation, it is important to also consider structural factors and additional indicators like the multicenter index (MCI) [54][55][56][57]. Thus, from now on, we will evaluate the aromaticity of heterocycles solely using the

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• ; Introduction 1,2-Benzoquinones represent unique building blocks for various classes of heterocyclic systems. Their structure depends on the reactivity of the initial heterocycles and 1,2-benzoquinones, as well as on the reaction conditions. In the series of 2-methylquinolines [1], 2-methylquinoxalines [2], 2

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• significant attention for their unique photophysical characteristics and versatility in NIR-driven reactions [51]. Cyanins consist of nitrogen-containing heterocycles connected by a polymethin chain [52][53], whose synthesis and modifications have been widely explored [54][55][56]. Such compounds exhibit

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• structure was obtained, revealing certain geometrical features. Keywords: 2-amino-substituted heterocycles; cyanoacetamide; Gewald reaction; multicomponent reaction (MCR); pyrimidine; Introduction The term “net-zero carbon” is becoming increasingly common as we consider a future marked by a rising global

• (hetero)aromatic, bulky and linear amines with different substitution patterns. The compounds 2–4 were purified by recrystallization and employed as such (Scheme 2). To our great delight, the heterocycles 2–4 could successfully be subjected to refluxing formamide under neat conditions, instantly yielding

• anthranilic acid and B) access to heteroannulated pyrimidones by MCRs of suitably substituted heterocycles and formamide as C1 source. Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Diversity and complexity were the essential features of our library of starting

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• . Review 1 Transformations via the formation of copper nitrenoids 1.1 C(sp3)–H amidation Lactams are recognized as one of the most significant nitrogen-containing heterocycles in drug discovery [69][70]. Among these, six-membered lactams, known as 2-piperidinones, have been extensively studied due to their

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• decreasing the oxidation potential. A range of functional groups, such as halides, ethers, and heterocycles, were tolerated well, yielding the corresponding enantioenriched products 14 with high enantioselectivity in the presence of chiral bisoxazoline ligand L2. A possible mechanism is depicted in Figure 5

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

• , Ankara 06800, Türkiye 10.3762/bjoc.20.273 Abstract Acenaphthylene-fused heteroarenes with a variety of five- and six-membered heterocycles such as thiophene, furan, benzofuran, pyrazole, pyridine and pyrimidine were synthesized via an efficient Pd-catalyzed reaction cascade in good to high yields (45–90

• total synthesis of the fungal natural product bulgarein. Keywords: acenaphthylene-fused heteroarenes; benzo[j]fluoranthenes; C–H arylation; fluoranthenes; heterocycles; Introduction An important subclass of polycyclic aromatic hydrocarbons (PAHs) [1] is comprised of fluoranthenes, which have been the

• heteroatoms or other heterocycles to obtain heterocyclic fluoranthene analogues offers numerous opportunities for structural and functional diversifications. For instance, azafluoranthenes such as triclisine (1) or imeluteine (2) constitute a common structural motif encountered in natural products isolated

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

• efficient and selective extraction of lanthanides and actinides and, furthermore, a number of heterocycles involving pyridine rings have been reported to exhibit biological activities [14][15][16][17][18][19][20][21][22]. We have recently reported, as shown in Figure 1, that the introduction of a multiply

• afford 8b in 89% yield under similar conditions, in which the result of carbocyclic amide (7a vs 7b) contrasted with the case of heterocyclic ones, 1c vs 3 and 5a vs 5b. Conclusion We have shown the facile synthesis of fused nitrogen-containing heterocycles and extended the scope of the intramolecular

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

• materials [1][2]. Due to their importance, different synthetic routes involving stoichiometric and catalytic approaches have been developed. The α,β-unsaturated imines, also known as conjugated imines or 1-azadienes, are useful precursors for the construction of aza-heterocycles. Due to their structure

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• reactivity compared to other alkynes, which typically require much shorter reaction times. Extending the reaction time provided a higher conversion to the product 14. Yields were observed to be greater for aryl azides (e.g., 4 vs 6). Heterocycles such as pyridine (1), pyrimidine (10), phenothiazine (11), and

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray). Keywords: fluoroalkyl groups; heterocycles; hydrazino acids; peptides; tetrahydropyridazines

• , the tetrahydropyridazines, six-atom nitrogenous heterocycles, are found in various bioactive molecules such as influenza virus neuraminidase inhibitors, GABA type A receptor modulators, and regulators of progesterone receptor or cannabinoid CB1 receptor antagonists (Figure 1) [6][7][8][9]. This

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• ; heterocycles; hypervalent iodine; oxidation; Introduction Halogenated carbocyclic and heterocyclic compounds are present in many active pharmaceutical ingredients [1][2]. The intramolecular halocyclisation of alkenes mediated by HVI(III) reagents allow access to a range of halogenated cyclic scaffolds in a

• -, stereo-) of the reaction, which is influenced by the type of HVI reagent, the nature of the substrates employed and the proposed mechanism from the authors are all described. The halocyclisation of alkenes to make halogenated carbo or heterocycles is yet to be covered by a review, which is the vacancy

• aza-heterocycles were synthesised in good yields. The authors proposed a mechanism for the fluorocyclisation reactions (Scheme 6), which relies on the activation of the fluoro-iodane reagent 12 with the zinc catalyst. The activation enables better orbital overlap to occur with the π bond of the alkene

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

• –acceptor (EDA) complex. The complex is formed of triphenylphosphine, sodium iodide and N,N,N,N-tetramethylethylenediamine (TMEDA) with diaryliodonium reagents (DAIRs) [64]. This activates DAIRs 16 to generate an aryl radical which is utilized in the C–H arylation of various heterocycles 31 to yield the

• the aryl ring which is less sterically hindered. The reaction conditions enabled to furnish results with various aromatic and nonaromatic heterocycles and N-heterocyles. The reaction was able to facilitate late-stage diversification of drug molecules such as nimesulide and gemfibrozil to corresponding

• 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 pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• compounds with antibiotic, antiviral, and anticancer properties that are found in many drugs and natural products [1][2][3][4][5][6]. Pyrroles' biological properties manifest when they are fused to other heterocycles [7][8][9][10][11][12]. Among them, seven-membered heterocycles of the benzodiazepine

• /benzoxazepine/benzothiazepine is very important. Due to the wide applications of pyrrole-fused heterocycles, very diverse approaches have been developed for their synthesis [28][29][30][31][32]. In recent years, multicomponent reactions (MCRs) have emerged as one of the most efficient and powerful methods to

• QS (quinine sulfate) (a); emission for 4a, 6c and QS (b); c = 75 ppm in ethanol and T = 298 K. Methods for the construction of pyrrole-fused heterocycles through I-MCR reactions. The model reaction of dibenzoxazepine, gem-diactivated olefin (2-benzylidenemalononitrile), and cyclohexyl isocyanide

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• anticancer activity of these compounds. Keywords: cancerostatic activity; carbohydrates; heterocycles; N-glycosides; indirubin; Introduction Indigo (1a), known for more than 6000 years and originally produced from indigo plants in India, represents a famous traditional blue pigment which was an expensive

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• ethynylethylene carbonates and copper catalysts (Scheme 37). He et al. [77] completed formal [4 + 1] and [4 + 2] annulations and obtained two types of seldomly studied heterocycles of thieno[2,3-c]pyrrole (Scheme 38, 36a–j) and thieno[2,3-d]pyridazine (Scheme 39, 38a–h) in high yields. It is worth noting that the

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

• efficient methods for the synthesis of heterocycles by multicomponent processes and domino reactions [16][17][18][19][20], here we disclosed the oxidative one-pot four-step synthesis of 2-amino-3,3’-spiroindolenines using readily available tertiary amines, electron-rich anilines and isocyanides as starting

• 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

• and t-BuNC conducted under optimized conditions. Synthesis of spiro[indole-heterocycles]. Synthetic strategy for the new synthesis of 2,3-diaminoindolenines [21] and spiro[indole-isoquinolines]. Scope of the synthesis of spiro[indole-THIQs]. aα-aminoamidine 2b has been isolated (54%) too; bα

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• was studied by UV–vis and fluorescence spectroscopy. Keywords: cross-coupling; cyclization; heterocycles; palladium; Introduction Nucleobases contain the coded information and give DNA and RNA their typical structure. As a nucleobase, uracil is involved in numerous vital processes and is therefore a

• reactions (Figure 1). Polycondensed heterocycles containing a uracil moiety have also been studied in recent years. For example, compound A exhibits antitumor and antimicrobial properties (Figure 2) [66][67]. Compounds A and B are used as starting materials for the synthesis of polyaromatic derivatives of

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluoroalkenes could be synthesized by applying other cross-couplings to 2. In addition, enynes 3 could be converted into derivatives, such as fluorine-containing alkynylalcohols [47], allene compounds [48][49][50], and heterocycles [51][52]. However, further experiments are required to expand the abilities of 2

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• have identified effective modifications of peroxydisulfate-mediated oxidation reactions that allow us to obtain hydroxylated nitrogen-containing heterocycles in high yields. Our laboratory is currently investigating the application of these modifications to the oxidation of compounds of different