Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• C14 β-OH group. The revised synthetic route is described in Scheme 2. At first, 4 was subjected to a Pd/C-catalyzed hydrogenation to afford the desired A/B-cis fused intermediate 7 along with its C5 epimer as a 2:1 separable mixture in a quantitative yield. By treating 7 with the Bestmann ylide

• -catalyzed anaerobic conditions [30], 11 was transformed into the C14 hydroxylated intermediate 12 as epimeric mixture in 42% yield and dr = 1:5, among which the undesired 14α-hydroxy epimer was the major component. Interestingly, the use of Co(acac)2 or Mn(acac)2 as the catalyst [31][32] instead of Fe(acac

• -carbonyl reduction by dissolved lithium metal in liquid NH3 solution, and the C11 α-hydroxylated intermediate 13 was obtained as a single diastereoisomer in 54% yield. Lastly, as expected, a Co(acac)2-catalyzed Mukaiyama hydration of 13 afforded the desired natural product sarmentogenin (2) in 69% yield

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• heterocyclic aldehydes such as furfural (3v), thiophene (3w) and indole (3x) carboxaldehydes. Application of the optimized EDA-catalyzed Knoevenagel conditions to thiazolidine-2,4-dione (2b) afforded the expected product 4a in moderate yield (Supporting Information File 1, Table S1). Adding excess thiazolidine

• transformations. The EDA-catalyzed Knoevenagel condensation reactions performed well even when a 10-fold increase in scale was applied (Supporting Information File 1, Scheme S1). The overall reaction profile was very much alike the smaller scales, affording the products in excellent yields (96–97%). A proposed

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

• ], Enders [21], Rafinski [22], Scheidt [23], Connon [24], Chi [25], Milo [26][27], Gravel [28][29] and others [30]. These NHC-catalyzed developments have drastically improved the achievable diastereo- and enantioselectivity, including common named reactions such as benzoin reactions, Stetter reactions

• ][47][48][49][50]. This review focuses on recent synthetic developments of NHC-catalyzed, visible-light-promoted dual organophotocatalysis for preparing carbonyl compounds and related organic intermediates by combining NHC and organic photocatalysts. Organocatalysts have a significant impact on the

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• enantioenriched compound 33, a nickel-catalyzed hydrocyanation of the terminal alkyne was performed. Subsequent protection of the tertiary alcohol with TESOTf and reduction of the resulting cyanide to an aldehyde afforded compound 34 (Scheme 4). Addition of isopropenyllithium to aldehyde 34, followed by TES

• deprotection and oxidation of the secondary alcohol, yielded the cyclization precursor 35. A B(C6F5)3-catalyzed tandem Nazarov/ene cyclization of 35 provided the key spirocyclic intermediate 37. The tertiary alcohol was protected in situ with TESOTf to suppress retro-aldol side reactions. Notably, prior TES

• deketalization afforded carbonate 58. A palladium-catalyzed decarboxylative alkenylation reaction was then carried out across the less hindered face of the six-membered ring to connect C5 and C6. Selective deprotonation and triflation at the C4 carbonyl group provided enol triflate 59. An intramolecular

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• ) studies. Conversely, the “biomimetic synthesis” strategy mimics nature’s enzyme-catalyzed pathways to construct target molecules in the laboratory, offering milder reaction conditions and more concise synthetic steps, while demonstrating excellent atom economy and step economy [5][6][7]. These powerful

• reaction with allyltributylstannane, yielding compound 40. After isomerization of the C11 allyl double bond and introduction of a C6 isobutenyl group, the resulting diene 42 underwent RCM catalyzed by the Hoveyda–Grubbs catalyst to form the pentacyclic skeleton 43, thus completing the C ring of the natural

• adduct was subjected to AgOTf-catalyzed lactonization to successfully construct the D ring of target molecular framework. Next, a 1,4-addition reaction introduced a vinyl group to compound 68, affording compound 70. A Pauson–Khand cyclization of 70 under [RhCl(CO)2]2/CO conditions smoothly furnished the

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

• (2) and C (3), featuring a visible light-catalyzed radical cation cascade for the formation of the C8–C8′ and C2–C7′ bonds [6]. Subsequently, they improved the reaction conditions to achieve the racemic synthesis of aglacins A (1) and E (4) as well [7]. In 2021, the Gao group described the total

• synthesis of both enantiomers of aglacins A (1), B (2), and E (4) by asymmetric photoenolization/Diels–Alder reactions as the key steps for the construction of the C7–C8 and C7′–C8′ bonds [8]. During the past decade, we had developed nickel-catalyzed or -promoted reductive coupling/cyclization reactions for

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• phenanthridines, naphthyridines, and phenanthrolines were prepared via Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles. Analogs with triazole N1-connected ortho-bromobenzene subunits successfully underwent annulation under microwave irradiation in yields of 31–90%. In contrast, annulations of triazole C1

• tandem deprotection/click chemistry followed by Pd-catalyzed annulation is summarized in Table 1. The alkyne-substituted analogs 1–6 [48][49][50][51][52] used in this study were prepared from commercially available aryl halides using microwave-promoted Sonogashira coupling (Table S1, Supporting

• modification of the base-catalyzed conditions reported by Kwok [53], where a stoichiometric plus additional catalytic amount of tetraethylammonium hydroxide base in DMSO solvent was used to promote tandem trimethylsilyl deprotection and cycloaddition in one preparation (Figure 3). Isolated yields of this

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

• challenging due to the inherently higher reactivity at the C3/C6 positions. In this study, we report a palladium-catalyzed, directing group-assisted, regioselective C1–H nitration of carbazoles. The protocol features a removable directing group and is amenable to gram-scale synthesis. This strategy provides a

• methodologies are greatly limited due to harsh reaction conditions that impact the scope of the reaction, poor yield, and regioselectivity issues. In sharp contrast, transition metal-catalyzed cross-coupling reactions promisingly improve the regioselectivity issues and substrate scope [25][26][27][28]. In

• addition to cross-coupling reactions, transition metal-catalyzed cyclization involving C–H activation approaches have also been reported [29][30][31][32][33][34][35][36]. Despite the significant advances in carbazole core constructions, the established protocols significantly lack access to selectively C1

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• formation of unique radical intermediates [9][10]. We previously demonstrated the Ir-catalyzed [2 + 2] cyclization/retro-Mannich reaction of a tryptamine-substituted cyclopentenone F, which led to the formation of indoline J (Figure 1b) [15]. Unlike other reported methods [16][17][18], the PET reaction of F

• construction of the tetracyclic core of Aspidosperma alkaloids. Our method involves an Ir-catalyzed PET reaction of K for the stereoselective formation of the cis-configured BC bicyclic core with an all-carbon quaternary center [25][26]. Computational studies suggest that the observed tandem PET reaction of K

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• was the p-methoxy derivative 11 which, as expected, was more reactive and hence more difficult to purify due to decomposition on silica gel. The p-methoxybenzyl trifluoroacetimidate (9) has been shown to be an effective regent for the acid-catalyzed benzylation of alcohols [12][30]. Conclusion In

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• axially chiral selenium-containing compounds by the formation of C–Se bonds is reviewed from three aspects. Review 1. Catalytic atroposelective synthesis of selenium-containing atropisomers by transition-metal-catalyzed C–H selenylation reactions Transition-metal-catalyzed enantioselective C–H activation

• has emerged as a powerful strategy for the rapid synthesis of functionally enriched axially chiral diaryl compounds. However, due to the potential strong coordination between organoselenium compounds and transition metals, the direct construction of C–Se bonds via metal-catalyzed C–H bond

• formation proceeded through an SN2-type nucleophilic substitution mechanism (Scheme 1). In 2025, Li and co-workers reported a highly efficient rhodium-catalyzed enantioselective C–H selenylation reaction of 1-arylisoquinolines with diselenides, employing 3,5-(CF3)2C6H3CO₂Ag and AgSbF6 as additives [19

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• aldehyde 53 [39] (Scheme 10). The key steps in this synthesis are based on an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction [40], followed by a unique benzilic acid-type rearrangement under very mild conditions [41]. A step-by-step mechanism for the benzilic acid-type rearrangement of

• available (+)-sclareolide (101) as starting compound, from which key alcohol 102 was synthesized in 7 steps. Selective mesylation of the secondary alcohol in 102 followed by semipinacol rearrangement catalyzed by t-BuOK afforded diketone 104 as a pair of epimers at C12 in a 1:1 ratio, with 70% overall yield

• ] described the first total syntheses of racemic meroterpenes (±)-andrastin D (106), (±)-preterrenoid (107), (±)-terrenoid (108), and (±)-terretonin L (109) using a Co-catalyzed homoallyl-type rearrangement/hydrogen atom transfer (HAT) as ring contraction strategy. Radical hydrochlorination of olefin 110 [57

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• aqueous environment, it was possible to obtain the associated products resulting from the cycloaddition reactions of non-hydrophobic nitrones with ethyl cinnamate derivatives. These products were achieved with a yield of 78–85% within 12 hours, operating at 100 °C under conditions catalyzed by γ

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

• -arylindoles with α,β-unsaturated ketones, followed by Fe(II)-catalyzed spirocyclization of readily accessible oxime acetates. The method exhibits a broad substrate scope and good functional group tolerance. The synthesized spirocyclic compounds showed no significant antimicrobial activity. Keywords: α,β

• cyclization. Subsequently Zhong et al. reported a catalytic asymmetric variant, affording spirooxindoles in high yields with excellent enantioselectivity [8]. An alternative approach employing vinyl azides involves a Rh(II)-catalyzed olefination of diazo compounds, followed by annulation with vinyl azides to

• yield substituted spiropyrrolidines (Scheme 1, path b) [9]. Additionally, an organocatalytic, enantioselective Michael addition/cyclization sequence of 3-aminooxindole Schiff bases with terminal vinyl ketones, catalyzed by a cinchona-derived base, has been reported to afford chiral spiroindolylpyrroles

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• featuring a novel Pd-catalyzed β-lactone formation [29]. In addition to these approaches, Nelson and co-workers reported a very concise and impressive total synthesis of vibralactone involving photochemical valence isomerization of substituted pyrone, cyclopropanation, and ring expansion [30]. Zeng, Liu and

• co-workers investigated the biosynthetic pathway of vibralactone (6). They established that 4-hydroxybenzoate serves as the direct ring precursor of vibralactone and the β-lactone moiety was formed via vibralactone cyclase (VibC)-catalyzed cyclization [31][32][33][34]. This is a fascinating

• single step from commercially available fructone [38] (Scheme 3). Following an efficient O-trimethylsilylquinine-catalyzed ketene–aldehyde cycloaddition and subsequent alkylation [36], 17 was synthesized. From 17, it was envisioned that the bicyclic skeleton could be efficiently constructed through ketal

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

• total synthesis – 2010 In 2010, Siegel and co-workers reported their total synthesis of complanadine A (Scheme 2). Their synthesis centres on two transition metal-catalyzed alkyne–alkyne–nitrile [2 + 2 + 2] cycloadditions to forge the two pyridine rings encoded by complanadine A [21]. Notably, the C2–C3

• , 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

• reaction to rapidly establish the tetracyclic skeleton of complanadine A and an iridium-catalyzed site-selective pyridine C–H borylation followed by a Suzuki–Miyaura cross coupling to forge the C2–C3’ linkage. Their synthesis achieves a high degree of synergy between classic transformations and modern

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• moderate diastereoselectivity; this was followed by Mn(III)-catalyzed metal-hydride hydrogen atom (MHAT) transfer to reduce the endocyclic olefin, forming 41 as a single diastereomer. Subsequent transformations – including a Wittig reaction, demethylation, and oxidation of the resulting phenol to a p

• Norrish–Yang cyclization, followed by a strain-release Pd-catalyzed C–C cleavage/cross-coupling protocol [9][11]; the strategy was subsequently applied to the total synthesis of lycoplatyrine A (89) in 2021 [38]. Isolated by Low’s group [39], lycoplatyrine A (89) belongs to the lycodine-type Lycopodium

• 82, followed by dehydrogenation, delivered compound 83 in 49% yield over three steps. Pyridone 83 could be funneled into pyridine 85 through O-triflation followed by Pd-catalyzed reductive detriflation. Ir-catalyzed meta-selective C–H borylation of 85, followed by bromodeborylation of the pyridine

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• ]. Next, we performed the oxidative coupling reaction of 1 and W4 in CH2Cl2 catalyzed by anhydrous FeCl3 to give W1 in 35% yield [45]. For the synthesis of W2, we first oxidized triphenylene with CrO3 and 18-crown-6 to give triphenylene-1,4-dione (2) according to Echavarren’s protocol [46]. Triphenylene

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

• of alkenyl halides 7a and 7b with the green oxidant H2O2 gave trace conversion after 3 days; however, the reaction using m-CPBA catalyzed with p-TSA was complete in 24 hours and afforded the halogenated lactones 8a and 8b in 33% and 34% yield, respectively (Scheme 1). We have recently reported the C3

• 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

• research on auxiliary-based chiral Lewis acid catalysis inspired Porter, Sibi and others to transpose the concept to radical chemistry. A large number of enantioselective radical reactions that were reported during 1996–2007 were mainly based on chiral Lewis acid-mediated/catalyzed free radical reactions

• ], ion pairs [15], N-heterocyclic carbene (NHC) catalysts [16][17][18], or thiols [19][20][21] are not covered here but can also be effective for achieving high levels of enantioselectivity in radical reactions. Lewis acid-catalyzed radical reactions In the context of enantioselective radical reactions

• ) [40]. The reactions were catalyzed by chiral Lewis acids and involved conjugate addition of a nucleophilic alkyl radical to an α,β-unsaturated substrate containing an oxazolidinone or pyrrolidinone template. The resulting α-radical was trapped with an allylstannane and the addition and trapping

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

• transition states. This integrated control framework provides a rational basis for designing reaction conditions to optimize selectivity and efficiency in organic synthesis. In 2014, the Liu group developed an Au(I)-catalyzed cascade cyclization strategy for synthesizing polysubstituted naphthalenes using

• dual roles as solvent and nucleophile, the gold-catalyzed intermolecular Markovnikov addition of methanol to the gold-activated alkyne proceeded to afford dienol intermediate 4. The intermediate 4 subsequently underwent a regioselective 6-endo-trig cyclization, generating the naphthalene core 7 (Scheme

• regioselective syntheses of indene, indenone, and naphthalene derivatives from simple aromatic 1,5-enyne substrates. In 2020, a solvent-controlled strategy for Au(I)-catalyzed divergent syntheses of phenanthrene and dihydrophenanthrene derivatives was developed by the Rodríguez group (Scheme 3) [10]. In

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• series of molecules: the ones without chlorine in meta position on this group (series a) and the others which kept this chlorine, like in DB18 (series b). These syntheses are reported in Scheme 2. A Suzuki-type Pd-catalyzed coupling of 7a with 4-(methoxycarbonyl)phenylboronic acid dimethyl ester (8) gave

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

• regioselectivity issues, multistep procedures, and limited applicability to tetra-ortho-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C–N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and

• intricate and inefficient using these standard synthetic protocols. The transition-metal-catalyzed C–N bond formation has emerged as a viable route to access non-symmetric azobenzenes, owing to the broad functional group tolerance of Buchwald–Hartwig amination reactions [34][35][36][37][38][39][40]. Kong

• hydrazines. Their method involved a three-step process comprising Cu and Pd-catalyzed C–N bond formations followed by a dehydrogenative deprotection step (Figure 1b, top) [42]. This desymmetric approach was further employed by Oestreich and co-workers in 2022, who introduced silicon-masked diazenyl anions in

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

• the indole frame (Scheme 2) [185]. In the presence of KPF6 and NaOAc, subjection of alkyne 3 and aniline 4 to [RuCl2(p-cyneme)]2-catalyzed electrochemical annulation formed the titled indole 5 successfully. After studying the reaction in details, the best reaction conditions were acquired as following

• , 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

• 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