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

• 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

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

• copper catalyst was still required in that procedure. In 2023, Bera presented an electrochemical oxidative [3 + 2] cycloaddition of secondary propargyl alcohol to access 1,2,3-triazole (Scheme 19) [273]. After probing the reaction systematically, the optimal conditions were presented as following: a

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

• 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

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

• techniques, indicating that the observed arylation–cyclization cascade reaction is highly stereospecific. With this result in hand, we performed copper catalyst screening (Table 3). We observed that CuCl and the CuOTf benzene complex gave similarly good yields (82–84% by NMR, Table 3, entries 2 and 4), while

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

• on developing a new additive-free protocol, catalysed by a copper catalyst supported on acidic zeolites that efficiently catalysed C2-benzoxazole amination in the presence of a perfluorinated solvent (hexafluoroisopropanol) as a source of mobile protons. Despite the significant interest in this area

• reaction conditions both in terms of temperature and time, as observed using a lower catalyst amount. This assumption was confirmed when the reaction was performed in a MW reactor under 5 bar of N2; in this environment, the copper catalyst cannot regenerate because of the absence of oxygen (see mechanism

• 2a-o and underscore the critical role of copper in catalysing the synthetic process (Table 3, entries 11 and 12). We believe that the exceptional performance of the solid-supported copper catalyst, which was even superior to homogeneous CuCl in terms of product purity and conversion, can be

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

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• radical was detected by HRMS, which supported a radical mechanism. Next, the influence of the atmosphere and the role of copper catalyst was evaluated (Scheme 4, reaction 2). Neither under argon nor under an oxygen atmosphere, the yield of 3a did not exceed 22%. However, employing 200 mol % of copper(II

• ) sulfate under an argon atmosphere afforded 3a in 33% yield. These results indicate, that copper(II) at high loading is capable of oxidizing H-phosphonate even in inert conditions [72]; however, a balanced concentration of oxygen in the reaction mixture is required for recycling of copper catalyst and

• oxides as PH-reagents. The developed protocol utilizes a simple copper catalyst under mild reaction conditions and synthetically available enol acetates (compared to traditionally employed alkenes, alkynes, cinnamic, and α,β-alkynyl carboxylic acids). The present approach showed good functional group

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

• represents a highly challenging direct C(sp3)–H asymmetric amination. Mechanistic insights: When using a bulky, electron-rich chiral bisphosphine ligand L6, the glycine ester substrate coordinates with the copper catalyst to form a key intermediate complex Int-26. The sterically hindered and electron-rich

• the anionic cyano-substituted bisoxazoline ligand L7, the glycine ester and copper catalyst form a distinct intermediate complex Int-28. The ligand’s reduced steric bulk and altered electronic properties facilitate direct interaction with alkyl radicals, forming a high-valent Cu(III) intermediate Int

• influence of steric and electronic effects during the hydrometallation process, simultaneously achieving the synthesis of chiral α-quaternary carbon amino acid derivatives 26 and α-chiral β-amino acid derivatives 27. Using a copper catalyst, the chiral α-quaternary carbon amino acid derivatives 26 were

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• efficient, reusable heterogeneous catalyst for this cascade reaction, achieving good to excellent yields without any loss of activity even after ten cycles of simple filtration-based recovery [12]. Moreover, a copper catalyst has been shown to function effectively in both organic and aqueous media [13][14

• quinazolinones, and the wide application of the chitosan-supported copper catalyst in various organic transformations [19][20][21], the use of chitosan-supported copper for quinazolinone synthesis has not been reported. As part of our ongoing research interest in chitosan and chitosan-supported copper catalysts

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• centers [30][31][32][33]. Herein, we report a mild and efficient method for the regio- and (E)-stereoselective formal hydrocyanation of di- and trisubstituted allenes. Using DIBAL-H as the hydride source and TsCN as a readily available and bench-stable cyanating agent in the presence of a copper catalyst

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• , we conducted a 5.0 mmol scale reaction and obtained the target product 3aa in 82% yield (Scheme 3). Based on previous reports, a plausible mechanism was proposed. In the presence of a copper catalyst, aniline reacts with cyclobutanone oxime to form an imine intermediate, which undergoes isomerization

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

• only when aliphatic disulfides are used because of the higher Lewis basicity of the alkylated sulfur atom, which poisons the copper catalyst. When the reaction was carried out with paraformaldehyde and other solvents (such as DMF, 1,4- dioxane, toluene, and DCE) the yield was very low (between 0–34

• , in which the copper catalyst (CuCl, 15 mol %) only activates the C–H bond of the terminal alkyne, and the resulting nucleophile A reacts with the iminium ion F generated from CH2Cl2 and the secondary amine via an aminal intermediate E (Scheme 24) [68]. However, Yu et al. found no evidence for the

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

• ) nitrenoid intermediate INT-7. Subsequent nitrene insertion, protodemetalation, and intramolecular cyclization furnish the desired 1,2,4-triazole. 1.3 Three-component formation of N-acyl amidines In 2019, N-acyl amidines were prepared from dioxazolones using a copper catalyst with terminal alkynes and

• copper catalyst, providing the vinyl copper intermediate INT-30. This intermediate then undergoes oxidative addition to the N–O bond of the dioxazolone to generate INT-31. Subsequently, decarboxylative reductive elimination occurs, forming the copper imidate INT-32. The active copper species is

• was proposed for the copper-catalyzed synthesis of primary amides. Dioxazolone first binds to the copper catalyst, forming the dioxazolone-copper complex (INT-34). The silane reductant then reduces INT-34, forming the copper imidate radical species INT-35, furnishing the formation of primary amides 28

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

• terminal alkyne 2 in the presence of a chiral copper catalyst and base, which reacts with the electrophilic iminium intermediate 15 to yield the desired chiral product 14. Active Cu(I) is regenerated either through cathodic reduction or by reaction with TEMPO–H. A year after the Mei group’s report, the Xu

• pair (AQDS•−, 20•+) then generate a benzylic radical 23 and a semiquinone radical ([AQDS–H]•) through proton transfer. The benzylic radical intermediate 23 subsequently reacts with the chiral copper catalyst L3Cu(II)(CN)2 (25) to form a Cu(III) complex 26, which undergoes reductive elimination to

• produce a chiral product 22. The reduced copper catalyst 24 and [AQDS–H]• are reoxidized to L3Cu(II)(CN)2 (25) and AQDS at the anode, respectively, completing the catalytic cycle. In the same year, following a similar approach, the Liu group explored a Cu-catalyzed photoelectrochemical enantioselective

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• (GlassContour) equipped with columns of activated alumina and supported-copper catalyst (Q-5) before use. 1,4-Dioxane and methanol were distilled from sodium, and stored over 4 Å molecular sieves. Unless otherwise noted, materials were obtained from commercial sources and used directly without further

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• or radical (Figure 1). The latter is typically operative when the reaction is carried out under oxidative conditions, usually in the presence of O2 and TEMPO, involving the formation of radical species through single-electron transfer (SET) from a copper catalyst to a precursor. Subsequent addition

• some cases, activation of a carbonyl group by the copper catalyst to facilitate nucleophilic attack has also been reported. Moreover, both activations can be operative simultaneously. Since copper shows affinity either for multiple C–C bonds or polar functional groups, it seems the ideal tool for this

• inhibition of the reaction in the presence of TEMPO confirmed this hypothesis. The copper catalyst assisted in the addition step of the alkylsulfonyl radical X to the alkyne. The presence of 2-iodopropane as additive improved the yields. The role was unclear, but it might facilitate the conversion of the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• –peroxidation of unsaturated alkenes 43 using AgSCF3 and TBHP was realized in the presence of the copper catalyst (Scheme 18) [60]. The radical trifluoromethylthiolation of alkenes 43 triggers a 1,5-HAT and further recombination of the generated C-centered radical with the tert-butylperoxy radical to afford the

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

• copper catalyst afforded nearly better results for the arylated products. In 2022, Linde et al., demonstrated a conventional approach for achieving arylations of nitrogen- and oxygen nucleophiles via SNAr reaction, using o-fluorinated diaryliodonium salts 40, which enabled access to a greater range of

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• chlorides in the presence of a copper catalyst to afford the corresponding tetrafluoroethylenated ketones 19. The ketones were then condensed with (R)-1-phenylethylamine under the influence of TiCl4 [34][35] to prepare various optically active imines (R)-16 in high yields (Scheme 3). Based on the result of

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

• showed that the reaction exhibits a negative nonlinear effect, while the kinetic experiments indicate that a mono-copper catalyst might be involved in the rate-limiting step. They speculated that the observed nonlinear effect might arise from the existence of both the inactive homo-dimer of ligands and

• yne-allylic cation intermediate, followed by an intramolecular cyclization. The disparity in reactivity could stem from the chelation between acyclic 1,3-dicarbonyl enolates and the copper catalyst, enhancing γ-position attack in an intramolecular manner. Conversely, Meldrum's acid's rigid cyclic

• , followed by a Conia-ene cyclization. The absolute configuration of the products is controlled by the ligand, which further confirms the remote stereocontrol of the copper catalyst. They obtained a single crystal of dinuclear copper and confirmed that the catalytic efficiency of the single crystal is

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• secondary and tertiary substrates too. In 2012, Lectka reported a fluorination of mostly aliphatic C–H bonds that used a molecularly defined copper catalyst with a bis imine ligand, along with co-catalytic N-hydroxyphthalimide and a phase-transfer catalyst [51]. Although only a few benzylic substrates were

• yields quoted vs copper catalyst. Iron-catalysed intramolecular fluorine-atom-transfer from N–F amides. Vanadium-catalysed benzylic fluorination with Selectfluor. NDHPI-catalysed radical benzylic C(sp3)–H fluorination with Selectfluor. Potassium persulfate-mediated radical benzylic C(sp3)–H fluorination

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• , herein, we utilized a copper catalyst to activate the C–I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents

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

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

• a non-complexed copper catalyst formed during the transformation [24][51]. When iridium-based photocatalysts were tested, no product formation or only traces were observed (Table 2, entries 2 and 3). Using Ru(bpy)3Cl2·6H2O afforded 17% of 4a, a similar yield as with Cu(dap)2Cl with a reduced

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters. Keywords: β-carbonyl diazo; copper catalyst; fluoroalkyl diazo; Mumm rearrangement; unsymmetrical β-diacylamino

• reacts with the copper catalyst generating the Cu-carbene intermediate B, which undergoes nucleophilic attack by acetonitrile to form the intermediate C. Subsequently, nucleophilic addition of benzoic acid to intermediate C affords the acetimidic anhydride D with the release of CuI catalyst for the next

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• DBDA in a one-pot manner. In the first reaction, o-phenylenediamine (1a) and 2-bromophenylboronic acid (7) were reacted in a pressure flask under an inert atmosphere using copper iodide (CuI) as the copper catalyst, Et3N, and Mo(CO)6 as CO surrogate in the presence of Pd(OAc)2/XantPhos as catalytic

• (1a), followed by the oxygen-promoted insertion of the phenylboronic acid coupling partner 7 to deliver intermediate II that undergoes reductive elimination to give diarylamine 3a along with regeneration of the copper catalyst (Scheme 5). Then, a palladium-promoted oxidative addition of the C–Br bond