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

• ureas 1 proceeded smoothly in an undivided cell (reticulated vitreous carbon (RVC) anode, Pt cathode, 5 mA), forming the desired indoles 2 in high yields. The reaction showed good compatibility with various functional groups like phenyl, furyl, alkenyl and alkyl at the acetylene moieties, producing 2a–d

• reversible C–H activation to give the six-membered intermediate C. Substitution of the acetate ligand in C by 3 caused the generation of complex D. The six-membered ruthenacycle E was then obtained by migratory insertion of acetylene into the Ru–C bond. Finally, reductive elimination of E formed the target

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• 1,2,3-triazole derivatives were generally obtained with good to excellent yields (50–96%). Both electron-withdrawing (fluoro (3b) or trifluoromethyl (3c)) and electron-donating (methoxy, phenoxy, and alkyl (3d–h)) groups were tolerated on the acetylene reaction partner species. In accordance with

• synthesis of benzyl azide, detailed experimental procedures, and characterization of prepared compounds are reported in Supporting Information File 1. General procedure for click reaction in CyreneTM In a 4 mL screw-cap vial, 1.15 mmol of benzyl azide (1a), 1 mmol corresponding acetylene, 0.1 equiv Et3N

• bromine and 1.3 mmol NaN3 were dissolved in 2.5 mL CyreneTM and stirred at a given temperature. After a given reaction time, 1 mmol of the corresponding acetylene compound, 0.1 mmol of Et3N, and 0.01 mmol of CuI were added to the reaction mixture and reacted for a given time at a given temperature. The

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• acetylene production, was investigated. The catalyst was obtained by calcination of calcium carbide slag at 600 °C (CS600) and characterized by XRD and FTIR analysis. The transesterification reactions were carried out with primary alcohols, producing fatty acid alkyl esters in 51–99% yields, depending on

• industrially compatible catalysts is very narrow. The absence of an available large-tonnage catalyst is the principal limitation to the industrial production of commercially demanded esters. Calcium carbide slag, a waste product from acetylene production via hydrolysis of calcium carbide [49], was successfully

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• constructed by condensation of dialdehyde 160 with compounds 161–163 yielding diketones 164–166. Next, diketones 164–166 were subjected to nucleophilic addition reaction by lithiated triisopropylsilyl (TIPS) acetylene, followed by SnCl2-mediated reduction of the intermediate diols. Finally, azulene-embedded

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

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

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• , 4l, and 4m in dichloromethane (c = 1·10−5 M). Synthesis of 3a–h. Conditions: i) Br2 (1.0 equiv), Ac2O (1.5 equiv), AcOH, 25 °C, 1 h [25]; ii) aryl acetylene (1.2 equiv), Pd(PPh3)Cl2 (5 mol %), CuI (5 mol %), NEt3 (10 equiv), DMSO, 25 °C, 6 h [26]. Yields of isolated products. C–N cross-coupling

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• team designed a new class of acetylene carbonate reagents and successfully applied them to copper-catalyzed decarboxylative amination/hydroamination sequences (Scheme 18) [48]. By controlling acidic and basic reaction conditions, the authors achieved the controllable synthesis of two types of

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• were observed. However, purification was not possible. Furthermore, an alternative commonly used synthetic strategy involving the Diels–Alder reaction of a pre-functionalized push–pull acetylene with furan or pyrrol derivatives proved unsuccessful [4][43]. All synthesized NBD derivatives were

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• -substituted terminal alkynes 42, including the industrially relevant acetylene and propyne. Interestingly, switching to the ligand (S,S)-Ph-BPE (L1) resulted in the asymmetric 1,2-difunctionalization of aryl-substituted terminal alkynes 42. The high levels of regio- and stereoselectivity achieved under mild

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

• theory (DFT) calculations, a proposed reaction mechanism is suggested as shown in Figure 3. Initially, copper acetylide INT-11 is formed by the reaction of acetylene with a copper precatalyst, leading to the formation of an N-acyl nitrene acetylide intermediate INT-12 after the incorporation of

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

• benzyl azide and triethylgermanyl acetylene (see Supporting Information File 1). The most effective conditions were found to be based on the classical combination of CuSO4/NaAsc, with optimisation (see Supporting Information File 1) delivering the general conditions shown in Scheme 2. These afforded a

• motif (Scheme 2b), and with variation of both components (Scheme 2c). In general, the CuAAC process worked effectively, tolerating the functional groups for which the CuAAC is well-known – in all cases the remaining mass balance was accounted for by the germanyl acetylene, suggesting sluggish CuAAC

• and the starting material could be recovered in each case, consistent with observations by Lam and MacMillan [71][72]. Variation of the steric and electronic parameters of the germanyl acetylene was straightforward (14–17; Scheme 2b). Several limitations were observed (Scheme 2d): benzyl azides

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

• or ester substituent. Firstly, the group of Haupt reported the synthesis of ethyl esters of tetrahydromethylpyridazine in 20% yield in a mixture of methanol and water by the reaction of methylhydrazine with acetylene dicarboxylic esters through the formation of enhydrazine (Scheme 1a), [23]. Later

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• integration of an acetylene bridge between the arene core and the norbornadiene units in compounds 1h–n may induce these effects. Herein, we present the synthesis of these target molecules and our studies of their photochemical and physicochemical properties with a focus on energy conversion and storage

• derivatives, and is, thus, more pronounced for the naphthalene-bridged compounds. Likewise, the increased size of the conjugated π-system also led to a red shift of the absorption bands in comparison with the ones of the corresponding norbornadiene derivatives without acetylene bridges (1b,e) [29][30

• )2 and the corresponding arylnorbornadienes without an acetylene bridge, such as 1o, leading to efficient and quantitative conversion to the quadricylanes (Scheme 4) [38]. Hence, we assumed that triplet-sensitized isomerization of the mono-, bis-, and tris-norbornadiene derivatives with an

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

• addition to the application of isocyanides in a variety of MCRs, one of the unique reactions involves the formation of zwitterions from isocyanides upon reaction with acetylene and active olefin compounds such as alkyl acetylenedicarboxylates and gem-diactivated olefins. Due to having nucleophilic and

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• it with our known iodonium species in the activation of Au(I)–Cl bonds. Results and Discussion As immediate precursor to the target structure 7Z, the literature-known isoxazole 10 was synthesized via a Cu(I)-catalyzed cycloaddition between (2-iodophenyl)acetylene (8) and benzyl nitrile oxide, which

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• (R = EWG-C6H4, E = PhS and PhTe) in moderate to high yields [30]. Very few examples of intermolecular cascade reactions with imidoyl radicals as key intermediates have been reported. The intermolecular cascade reaction of diselenide, electron-deficient acetylene, and isocyanide under photoirradiation

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• . An advantage of this method for preparing 1,3,5-substituted pyrazoles is its tolerance towards a wide range of substituents. Trimethyl phosphite can be added to acetylene dicarboxylates 95 to generate a zwitterion that readily reacts with electrophiles. This zwitterion undergoes a rearrangement

• toluene [173]. N-Vinylimidazole, an alkene with a leaving group, was used to synthesize the 3-substituted pyrazoles 169 because, unlike acetylene, it is not gaseous and, therefore, easier to handle. Instead of vinylimidazole, vinyl azides 170 can also be used as alkyne surrogates. After the 1,3-dipolar

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• all cases. All spirofuranones exhibited inhibitory activity on CYP3A, a well-known effect of steroids with an acetylene moiety at C-17. Additionally, compound 37 demonstrated vasorelaxant and bradycardiac effects when tested in precontracted aortic rings (Scheme 11). More recently, Nay’s group

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• of 87% and 64%, respectively. Unfortunately, the synthesis of vanillin (4q) was unsuccessful due to undesirable oxidation reactions of the electron-rich arene. The cyclopropane derivative 4r was generated from the cyclopropylmethanol in 53% yield. The acetylene derivative 4s could not be isolated due

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• be prolonged from 6 to 24 h and the amount of acetylene was increased. Thus, tris-alkynylated quinolines 12a–g were prepared in good 64–75% yields (Scheme 6). The yields of products 12a–g were lower as compared to bis-alkynylated products 6a–g which were, in fact, found as major side-products, due to

• %), acetylene (3.0 equiv), dioxane, NEt3, 100 °C, 6 h; isolated yields. Synthesis of 8. Reaction conditions: i: polyphosphoric acid, 150 °C, 2 h [33]; ii: POBr3 (1.1 equiv), 150 °C, 2 h. Synthesis of compounds 9a–g: Reaction conditions: Pd(PPh3)4 (2.5 mol %), CuI (5 mol %), acetylene (3.0 equiv), dioxane, NEt3

• , 100 °C, 6 h, isolated yields. Synthesis of starting material 11. Reaction conditions: i: AcOH, Br2 (1.1 equiv), reflux, 24 h; ii: POBr3 (1.1 equiv), 150 °C, 2 h. Synthesis of compounds 12a–g. Reaction conditions: Pd(PPh3)4 (2.5 mol %), CuI (5 mol %), acetylene (4.0 equiv), dioxane, NEt3, 100 °C, 24 h

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• steps (Scheme 15). The initial step involved the synthesis of compound 71 in 64% yield using a cobalt-catalyzed cyclotrimerization reaction between 1,2-diethynylbenzene (5) and bis(trimethylsilyl)acetylene (70), a method commonly employed in [N]phenylene synthesis. Subsequently, treatment of compound 71

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• a surrogate of acetylene reacted with trifluoroacetonitrile imine to form 1-aryl-3-trifluoromethylpyrazoles, followed by a series of cascade annulation/dehydration/ring contraction reactions when treated with p-TsCl [65] (Scheme 10b). The chemistry of pyrazoles with a fluorine or a fluoroalkylated

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

• beneficial to the reaction outcome than electron-rich groups in the phenyl ring (3a–f). The crystal structure of product 3i is shown in Figure 2. Also, substituents in different positions of the phenyl ring in acetylene 1 smoothly reacted with NaNO2 under the reaction conditions affording the products in

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• , including naphthalene cores, butadiyne and acetylene linkers. The main structural parameters of diynes 5 that characterize the degree of this distortion are presented in Table 2, where ϕ1 is the angle between the planes of the benzene ring and the neighboring naphthalene system, ϕ2 is the angle between the

• standard value of 180° by 3–10°. Deviations of bond angles in acetylene bridges are ≈1–7°. The methoxy derivative 5b has the most complex crystal packing with a large number of different nonvalent interactions (see Supporting Information File 1, Figures S62 and S63). The molecule of cyano derivative 5d is

• characterized by the least distortion of the DMAN fragments in the series (twisting Θ = 9.45 and 12.83°, torsions φA = 20.9° and φB = 8.4°, bond angle deviations in both butadiyne and acetylene linkers do not exceed 6°). In the crystal packing of 5d (see Supporting Information File 1, Figures S64 and S65), the

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• groups by using a CuAAC click reaction between azide and acetylene-substituted porphyrins in good yields as shown in Scheme 21. The photophysical and electrochemical studies along with DFT calculations showed that these dyads possess suitable frontier orbital energy levels for the use as sensitizers in