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

• Seeun Lim Teresa Kim Yunmi Lee Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea 10.3762/bjoc.21.63 Abstract This study introduces a highly selective hydrocyanation method based on copper-catalyzed hydroalumination of allenes with diisobutylaluminum hydride, followed

• 98% yield. Ortho-bromoaryl-substituted nitrile 3m also underwent tandem amidation and copper-catalyzed cyclization, efficiently producing lactam 9 in a 98% yield. Scheme 7 illustrates a plausible reaction mechanism based on previous studies [34]. The process begins with the formation of NHC–copper

• , as it minimizes the allylic strain between the R and R'' groups. Conclusion In this study, we developed a highly regio- and (E)-selective formal hydrocyanation protocol for allenes using a copper-catalyzed hydroalumination/cyanation sequence with DIBAL-H and tosyl cyanide. This approach offers mild

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

• report the copper-catalyzed synthesis of tetrahydroquinoline derivatives via a domino reaction of aniline with cyclobutanone oxime. This method demonstrates a selective approach for generating bioactive tetrahydroquinoline scaffolds, which have broad applications in pharmaceutical chemistry. The reaction

• cyclobutanone oxime using a copper-catalyzed reaction under ambient air conditions (Scheme 1c). Results and Discussion With these considerations in mind, we explored the feasibility of synthesizing cyclobutane-fused spirotetrahydroquinolines (STHQs) through the reaction of arylamines with cyclobutanone oxime

• to generate an enamine intermediate. Subsequently, an intermolecular cyclization occurs between the enamine and imine intermediates, ultimately yielding the final target product through an aromatization process (Scheme 4). Conclusion In summary, we have developed an efficient and practical copper

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

• attention due to their unique properties in stereoselective allylic substitution. This review highlights recent advances in copper-catalyzed asymmetric allylic substitution reactions with chiral secondary alkylcopper species, encompassing several key strategies for their generation: stereospecific

• -catalyzed allylic substitution reactions [20]. To address these limitations, copper-catalyzed processes have emerged as a promising alternative. Copper-catalyzed allylic substitutions are distinguished by their unique inner-sphere mechanistic pathway, which enables the incorporation of hard, non-stabilized

• nucleophiles 5 that have conjugate acids with pKa values greater than 25 such as organolithium, organomagnesium, organozinc, and organozirconium reagents. This crucial distinction effectively expanded the scope of allylic substitution reactions beyond traditional boundaries. The evolution of copper-catalyzed

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• alcohol 19 was isolated in 89% yield. The copper-catalyzed replacement of the bromine substituent in 19 with a hydroxy group was achieved in the presence of a catalytic amount of oxalamide ligand I [13]. This transformation is critical for enabling further functionalization and the reaction conditions

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• provided the corresponding amino-substituted N-acetyl diazocine 21 (Scheme 1). Another option for carbon–heteroatom bond formation reactions are copper-catalyzed Ullmann-type reactions, which have already been applied to the parent diazocine [36][37]. The attempted synthesis of azide-functionalized N

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• involvement of a fluorescent intermediate in the cascade synthetic process. Keywords: cascade reactions; copper-catalyzed three-component coupling; gold-mediated 6-endo hydroamination; tandem cyclizations; tetrahydroisoquinoline alkaloids; Introduction The bis-tetrahydroisoquinoline (THIQ) alkaloid family

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

• amidation Recently, Cao and co-workers reported the copper-catalyzed synthesis of 1,2,4-triazole derivatives via an N-acyl nitrene intermediate [76]. As illustrated in Scheme 3, dioxazolones 4 and N-iminoquinolinium ylides 5 served as reactive substrates, leading to the formation of various polycyclic 1,2,4

• -triazole analogues 6. Both dioxazolones 4 and N-iminoquinolinium ylides 5 demonstrated excellent tolerance in this transformation. Notably, electron-rich dioxazolones exhibited slightly higher reactivity. The proposed catalytic cycle for the copper-catalyzed synthesis of 1,2,4-triazole derivatives is

• modular copper-catalyzed method for the synthesis of N-acyl sulfenamides 20 from dioxazolones 18 using thiols 19 via nitrogen–sulfur bond formation (Scheme 7) [92]. Secondary and tertiary thiols were highly effective in affording the corresponding N-acyl sulfenamides 20a–d. Moreover, the bioactive motifs

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

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

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

• was crucial for the formation of the organozinc reagent (Scheme 19) [36]. Spiro-2,3-dihydroquinazolinones 26 were formed exploiting a one-pot multicomponent reaction, using isatoic anhydride, ketones and primary amines. The isolation of the amide intermediate XXIII obtained by the copper-catalyzed

• process by using α-diazoketones, nitroalkenes and primary amines, in the presence of air as oxidant. The mechanism involved the formation of α-ketocarbene XXVI from α-diazoketone, able to react with the amine affording imine XXV after copper-catalyzed oxidative dehydrogenation. The subsequent [3 + 2

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

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

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

• -abundant, inexpensive, relatively stable, and low toxic. Copper-catalyzed asymmetric allylic [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and propargylic [23][24][25][26][27][28][29][30][31][32] substitutions are effective strategies for constructing new C–C and C

• catalytic center; finally, the selectivity affording E-enyne and Z-enyne product is also an issue to be addressed, and possible side reactions need to be suppressed (Scheme 2). In this review, we summarize the recent development of copper-catalyzed yne-allylic substitutions. It is worth noting that when we

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• in MeOH at room temperature with a short reaction time. Some of them were further functionalized with a 1,2,3-triazole ring via copper-catalyzed azide–alkyne cycloaddition (CuAAC) and deprotected with trifluoroacetic acid. Several hybrids were evaluated against six cancer cell lines, displaying GI50

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• aldehyde [10]. Latterly, Yamamoto utilized a 90% deuterated [D2]-isocyanide in a copper catalyzed [3 + 2] cycloaddition to afford a 60% deuterated [D2]-pyrrole [11]. The utility of the Leuckart–Wallach reaction towards the generation of isocyanides was first explored by Dömling [12], yet the use of such

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

• to 97%. The Sonogashira coupling can also be effectively integrated with the CuAAC (copper-catalyzed azide–alkyne cycloaddition) reaction, offering a powerful tool for synthesizing diverse molecular architectures. In a consecutive multicomponent reaction, pyrazoles were first presented in a

• heteroaryls other than thiophene under standard conditions. Schreiner et al. established a further protocol for the one-pot synthesis of pyrazoles, where the alkynoyl moiety is generated by copper-catalyzed carboxylation of terminal alkynes followed by alkylation with methyl iodide, forming propiolic acid

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• fractionated cell cultures of M. alba with 49 was followed by irradiation with 365 nm light to generate reactive carbene from diazirine. This sequence allowed the formation of covalent bonds between the synthetic probe and binding proteins. The resulting mixture was subjected to a copper-catalyzed click

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• the triazole unit via a copper-catalyzed azide–alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty new multi-substituted pyrazole–triazole hybrids. We also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In

• cholerae [13], show antimicrobial properties [14], and can act as P2X7 antagonists, a receptor involved in neuroinflammation and depression [15]. Pyrazolyltriazoles are most easily obtained via the copper-catalyzed azide–alkyne cycloaddition (CuAAC) from pyrazolyl azides (7 and 8). These are usually

• aromatic and aliphatic alkynes 20a–h in a copper-catalyzed azide–alkyne cycloaddition (CuAAC). All attempted reactions could be conducted under standard conditions using copper sulfate and sodium ascorbate in THF/water (depicted in Scheme 3 and Figure 2). For selected derivatives, 21sd and 21vg, crystals

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• interest [12][13]. The various approaches used for selenation of aromatic compounds include directed lithiation [14][15], copper-catalyzed selenation [16][17][18], and aromatic nucleophilic substitution reactions [19][20][21][22]. Electrophilic selenium reagents (e.g., phenylselenenyl bromide) have often

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• and Figure 2). Like the oxindole scaffold, 1,2,3-triazole is also considered a privileged unit in drug discovery since compounds having this structure have a broad spectrum of biological activities, and have been widely used to create anticancer drug candidates [24][25]. The copper-catalyzed azide

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

• diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C–I bond and esterification. The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives. The

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

• General procedure for copper-catalyzed multicomponent reaction of β-amino esters Into a flask were added amines 1 (0.4 mmol), acids 3 (0.1 mmol), CuI (20 mol %), and CH3CN (2 mL). Then, the mixture was stirred at room temperature under a nitrogen atmosphere and t-BuONO (0.4 mmol) was added dropwise

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.20.21 Abstract An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper

• -catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an

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

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• diverse dibenzodiazepinones via a copper-catalyzed C–N bond coupling between 2-halobenzoates and o-phenylenediamines leading to a key intermediate that undergoes an intramolecular N-acylation to afford the corresponding dibenzodiazepinone structure in high yields (Scheme 1b) [14]. Another innovative

• approach in the case of the synthesis 4a (47% vs 41%). Our mechanistic proposal is based on the information in previous reports by the groups of Bose [28], Watson [29], and Stahl [30]. Mechanistically, under basic conditions, the reaction is triggered by copper-catalyzed activation of o-phenylenediamine

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• -scale use. Therefore, novel bromination reagents and simple bromination approaches are still required to be established. Very recently, we reported a copper-catalyzed C5-bromination and difluoromethylation reaction of 8-aminoquinolines using ethyl bromodifluoroacetate as bifunctional reagent [30] and

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

• wormlike nanoparticles. In rotaxanes, the utilization of metal–ligand bonding involving CuI is a common strategy for immobilizing a thread moiety within a macrocycle. However, the efficacy of such a bonding is compromised when catalysts are used in stoppering reactions, e.g., the copper-catalyzed azide

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• complex obtainable via a straightforward synthesis, with improved solubility, concerning our previous Co(II) complexes [21]. Thus, the new Co(II) complex bears two 1-benzyl-4-(quinolin-2-yl)-1H-1,2,3-triazole (BzQuTr) units, that were obtained through a copper-catalyzed alkyne–azide cycloaddition (CuAAC

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

• reported [16]. In 2015, Yang’s group [10][17] reported the copper-catalyzed conversion of methylarenes into isoxazole derivatives with KNO3 as the source of nitrile oxide (Scheme 1, reaction 1). In 2019, Deng’s group [18] developed a three-component synthesis method of isoxazole derivatives using TBN as