Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• excess benzyl azide or phenylacetylene, taken as representatives, under copper(I) catalysis, resulting in the narrow-rim triazolated macrocycles. By removing the Boc protecting groups and involving the free amino groups in reactions with p-tolyl isocyanate, a series of narrow-rim triazolated

• conversion into diverse 1,4-disubstituted 1,2,3-triazole units under CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition) ‘click’ conditions [70][71][72][73]. The first implementation of the CuAAC approach for calixarene modification was published shortly after its introduction into chemistry in general

• affect the cycloaddition by, for instance, binding copper cations or counter anions, and thus their presence in the structures of calixarenes at the CuAAC step must be avoided. On the other hand, the unmodified amines may also contribute to undesired Cu(I) stabilization and complicate the CuAAC work up

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• propargylamines via A3-coupling reaction [21]. In analogy to a literature procedure [22], heating of radical 2a in a mixture of dimethylamine, formalin, and tetrahydrofuran in the presence of copper(II) acetate afforded the corresponding dimethylamino derivative 2f. To confirm the structure of the novel

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• helical chiral entities was reported by Wang and co-workers. They reported an organocatalyzed asymmetric synthesis of phosphorus-containing chiral helicenes enabled by dynamic kinetic resolution using copper and peptide-mimetic phosphonium salts, i.e. amino acid-derived phosphonium iodide and bromide as

• catalysts [33]. A domino reaction was developed, beginning with a PPS L2-catalyzed Michael addition of phosphine oxides 7 to nitro-substituted oxa[5]helicenes 6, followed by a copper-promoted aromatization. This sequence efficiently produced phosphorus-containing oxa[5]helicene derivatives 8 in high yields

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• available reagents is an important task. Recently, we have developed a copper(I)/rhodium(II)-catalyzed method toward two types of regioisomeric 2,5-dihydrothiophenes 1 and 4, containing an acetyl group [50]. In this work, to evaluate the synthetic utility of these compounds (the scope is presented at page

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• ). In 2006, Apotex reported the synthesis of alkenyl chlorides using POCl3 in the presence of triethylamine and a copper catalyst (Scheme 16) [69]. The preparation of compound 84 is of industrial significance due to its application in the synthesis of terbinafine (86), an antifungal agent. The reaction

• iodide or bromide by chloride. In the presence of a copper catalyst and tetramethylammonium chloride (Me4NCl) as the chloride source, alkenyl iodides and bromides were efficiently converted to the corresponding alkenyl chlorides. Importantly, the transformation proceeded with full retention of the double

• , catalyzed by a chiral copper complex generated in situ from CuTC and phosphoramidite ligand 361, furnished the corresponding enantioenriched alkenyl chlorides in high yield and with exclusive formation of the Z-isomer. A decade later, Fañanás-Mastral and co-workers demonstrated that alkenylcopper species

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• 3-position, a copper-mediated C–H activation of position 12 and subsequent protection of the introduced hydroxy moiety to give compound 25 (Scheme 6). Installation of the lactone moiety in 22 was carried out in a three-step sequence via a 1,2-addition of organocerium reagent 26 to the ketone

• substituted cyclopentenone motif 37. The authors report the reaction to favor the desired diastereomer and could further enrich the desired isomer by recrystallization. Final steps for this fragment included a 1,4-reduction of the enone motif via a copper hydride species, a Wittig reaction to install the exo

• , with the hydroxy group at C17 playing a crucial role trapping a cationic intermediate from this rearrangement. Starting point in this synthesis is again dehydroepiandrosterone (24), which was protected in 3-position with an acetyl group (Scheme 12). A copper-mediated C–H activation procedure to obtain

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• asymmetric conjugate addition was carried out [20][21]. The in situ generated aryl–copper(I) species was obtained under the action of CuBr·Me2S with Grignard reagent 8, and then added to a THF solution of the α,β-unsaturated acyl oxazolidinone 7 at −48 °C. This reaction demonstrated an excellent

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• and copper salts were examined as an oxidant to enhance the yield. Surprisingly, none of the tested silver salts afforded the desired product, while copper salts resulted in either trace amounts or a lower yield of 2a (Table 1, entries 4 and 5). We also evaluated inorganic oxidants, but these oxidants

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• under heating furnished chiral spiroindolylpyrroles in excellent yields and enantioselectivity (Scheme 1, path d) [11]. Moreover, a copper-catalyzed reaction of oxindole-derived alkenes with acetophenone O-acetyl oxime has also been employed to construct the spiroindolylpyrrole scaffold (Scheme 1, path

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• , followed by acetylation of the resulting propargylic alcohol afforded 17 which was further advanced to 18 via copper-catalyzed selective displacement of the propargyl acetate with benzylamine and hydrolysis of the primary acetate. The primary alcohol of 18 was activated with PPh3/CCl4, triggering an

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• using CF3 donors in copper-catalyzed [34], base- and Lewis acid-mediated reactions [35][36][37]. The reaction of enamine 9a with Togni’s reagent (18) and subsequent hydrolysis gave the substituted derivative 19 in 35% yield (qNMR) (Scheme 4). The yield was improved using the N-methylpiperazine-derived

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

• -photocatalysts [10][11][12] have been successfully incorporated into enantioselective radical reactions. The use of transition metals to catalyze enantioselective radical reactions can be considered a major advancement in the field of asymmetric catalysis. Several metals such as cobalt, nickel, copper, and

• titanium have been employed successfully to catalyze enantioselective radical reactions. Two earth abundant transition metals that have found extensive application in enantioselective radical reactions are copper and nickel. These metals, particularly Ni, can be used in radical–radical coupling reactions

• occurred in an anti fashion. Products were obtained with up to 97% ee via catalysis by complexes of magnesium or copper(II) with ligand L1. The absolute stereochemistry of the product could be controlled by a simple change from copper(II) to magnesium Lewis acids while using the same chiral ligand, thus

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

• 133 (Scheme 27, path b). Through precise acid catalyst selection, the reaction pathways were strategically modulated to afford efficient construction of both 1H-pyrrolo[2,3-d]carbazole derivatives and spiro[indoline-3,3'-pyrrolidin]-2-one derivatives. In 2019, the Ye group reported a copper-catalyzed

• stereospecific tandem cyclization of indolyl homopropargyl amides for the construction of bridged aza[n.2.1] frameworks (Scheme 28) [40]. The copper catalyst, acting as a σ,π-dual activator, induced a 5-endo-dig cyclization to form a vinylcopper intermediate 135. Subsequently, a protodemetalation process first

• copper-catalyzed tandem process initiated by endo-cyclization of indolyl homopropargyl amides, enabling atom-economical synthesis of therapeutically significant bridged aza[n.2.1] skeletons. Angle strain and configuration-controlled cyclization of 1,n-enynes In cyclization reactions, angle strain and

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• and co-workers developed a Chan–Evans–Lam-type oxidative cross-coupling reaction between N-arylphthalic hydrazides and arylboronic acids using copper catalysis [41]. Similarly, in 2003, Lee and co-workers introduced a desymmetrization approach employing simpler N=N precursors, specifically N-protected

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

• advantages over traditional copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions, including operational simplicity and the absence of metal contaminants, which is crucial for pharmaceutical applications. After having identified suitable reaction conditions of the Ugi–azide and click reactions for

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

• , this protocol was an efficient and sustainable approach to synthesize 2,3′-biindolyl atropisomers and could be potentially applied in manufacture of functional materials, bioactive molecules and chiral ligands. Construction of isoindolinones and indolizines An electrochemical and copper-catalyzed

• of 22 with Cu(OPiv)2 and the following anodic copper(II) oxidation provided copper(III) carboxylate intermediate B. Facile carboxylate-promoted C–H activation and ligand exchange with 23 formed the copper(III) species D, which underwent metalation/reductive elimination to generate intermediate E

• along with the formation of Cu(OPiv) which was transformed to Cu(OPiv)2 by oxidation at the anode. Finally, the cyclization of E afforded target isoindolone 24. Notably, this reaction was the first example of electrochemical copper-catalyzed oxidative cyclization of alkyne which was enabled by C–H

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

• promising strategy for sustainable energy development involves the electrochemical oxidation of biomass-derived feedstocks. Recent work by Shen et al. demonstrates that glycolic acid (GA), also referred to as hydroxyacetic acid, can be synthesized from glycerol (GLY) using a copper single-atom

• trans-4,5-diamino-cyclopent-2-enones and 2,4-diaminocyclopent-2-enones [186]. In 2021, Coelho and Afonso prepared a silica-supported copper catalyst (Cu/SiO2-N2) by impregnation with copper nitrate, and used it for the reaction of furfural with secondary amines (alkyl, cyclic and aromatic) to produce

• trans-4,5-diaminocyclopent-2-enones in hexane/isopropanol solvent mixture under continuous flow conditions (Scheme 56). The scope could be extended to 2-substituted trans-4,5-diaminocyclopent-2-enones by using 3-substituted furfurals [187]. A copper triflate-based analogous strategy was also reported

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• , LV-1006, Riga, Latvia 10.3762/bjoc.21.154 Abstract A novel copper-catalyzed arylation strategy for propargylsilanes utilizing diaryl-λ3-iodanes has been developed, enabling a cascade sequence involving 1,2-silyl migration and heterocyclization. The β-silicon effect facilitates the formation of

• synthetic potential of iodane-mediated carbofunctionalization under copper catalysis. Keywords: arylation reactions; copper-catalysis; iodanes; propargylsilanes; 1,2-silyl shift; Introduction Highly electrophilic hypervalent iodine(III) reagents are considered as arene electrophilic synthons, making them

• have been induced by addition of external halogen or selenium electrophiles and Brønsted acids. This encouraged us to develop a methodology involving a copper-catalyzed terminal alkyne arylation of propargylsilanes by diaryl-λ3-iodanes, followed by 1,2-silyl shift and terminated by nucleophile addition

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• of products in copper-catalyzed 1,4-addition of phenylmagnesium bromide, Giese reaction with 2-iodopropane, Simmons‒Smith or Johnson–Corey–Chaykovsky cyclopropanation, hydroboration reaction with 9-BBN, and Diels–Alders reaction with Danishevsky diene. Gratifyingly, it was found that vinyloxazoline S

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

• -catalyzed reaction proceeds with low diastereoselectivity. The significant difference in selectivity can be explained by the fact that, in contrast to the Ni(II)-catalyzed reaction depicted in Scheme 3, the copper(I) catalysis involves the coordination by the metal of both reaction partners, and the

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

• CyreneTM, as a biomass-originated polar aprotic solvent, could be utilized as an alternative reaction medium for one-pot copper(I)-catalyzed azide–alkyne cycloaddition (click or CuAAC) reactions, for the synthesis of various 1,2,3-triazoles under mild conditions. Nineteen products involving N-substituted-4

• methods, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the so-called click reaction [7], has received substantial attention for the selective synthesis of various 1,2,3-triazoles that are of utmost importance in the synthesis of biologically active compounds such as active

• -triazoles in a less toxic and recyclable medium could further control and reduce the environmental impacts of this synthetically very important transformation. Herein, we report a study on the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in CyreneTM under mild conditions. Results and

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• Elena Fernandez Jaesook Yun Departament de Química Física i Inorgànica, University Rovira i Virgili, Tarragona, Spain Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea 10.3762/bjoc.21.109 Keywords: copper; copper catalysis; Copper catalysis continues to thrive as

• one of the most dynamic and versatile areas of contemporary chemical research. Once viewed primarily as a cost-effective alternative to noble metals, copper has emerged as a powerful and versatile catalyst, capable of mediating a wide array of chemical transformations through both two-electron and

• single-electron pathways. This duality has enabled access to previously elusive molecular transformations, positioning copper at the center of modern synthetic strategy. This thematic issue captures the dynamic nature of the field, featuring five insightful Review articles and five original research

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

• completed in 1.5–2 h. A solid Cu(I) catalyst supported on aminated silica made the process cost-effective and heterogeneous, thus simplifying work-up and minimising free copper in solution. The catalyst was found to be regeneratable and reusable for up to eight cycles. The optimised method facilitated the

• 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

• environmental abundance, low cost and low overall toxicity. A wide range of aminating reagents have been utilised, including nitrogen electrophiles and amines in the presence of external or internal oxidants [27], in many types of copper-catalysed synthetic protocols. The direct copper-catalysed C–H amination

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