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

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

• -rich and electron-poor substituents. This reaction was carried out between arylcyclopropanes 5 and acyl fluoride 4 in the presence of NHC (10 mol %) and 4CzIPN (5 mol %). Mechanistic studies showed that the cascade proceeds via nucleophilic ring-opening of a cyclopropyl radical cation D with subsequent

• , acyl fluoride 4, and keto-ester 19 via NHC/photoredox cooperative dual catalysis, which includes a radical cascade process reported by Zhu, Feng et al. The organic photoredox dual catalysis enables sequential C–C(O)OR and C–C(O)Ar bond formation, in the presence of catalytic amounts of NHC and organo

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

• Zhao group employed a similar two-phase strategy to achieve the first total synthesis of the Ryania diterpenoid garajonone (8) in 2025 [56] (Scheme 10). Key achievements of this synthesis include: (1) application of palladium-catalyzed Heck/carbonylative cascade cyclization to efficiently construct 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

• of (+)-aglacin B, a typical aryltetralin natural product [23][24], was completed from 2,6-dimethoxyphenol. The key Ni-promoted reductive cyclization cascade of a β-bromo acetal with an allyl tether, smoothly established the tetrahydronaphtho[2,3-c]furan core of this molecule in a new fashion. The

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

• to acid 157 by UV-C, which occurred only in the presence of water (Scheme 29). In the work [83], it is shown that a vinylogous Norrish Type II cascade reaction can occur for unsaturated ketones substituted with cyclopropanes. Interesting results of photochemical ring contraction were described by

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

• categorized into two main approaches. The first involves cascade reactions featuring the formation of multiple bonds, including a pivotal spirocyclization step. However, these strategies typically require pre-functionalized starting materials and often result exclusively in substituted oxindoles. For example

• in high yields (Scheme 1, path c) [10]. Further expanding the scope of enantioselective approaches, a Michael/cyclization cascade reaction between 3-aminooxindoles and 2-enoylpyridines, catalyzed by a cinchonidine-based thiourea organocatalyst, was developed. Subsequent treatment with HCl in methanol

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

• finding highlights the importance of complanadine A’s pseudo-dimeric structural motif for its biological function. The Sarpong total synthesis – 2010 In the same year (2010), Sarpong and co-workers reported their total synthesis of complanadine A (Scheme 3). Their synthesis features a biomimetic cascade

• , which continued with an amide-ketone condensation to finally produce 31 in this highly efficient one-step biomimetic cascade sequence. The secondary amine of 31 was selectively protected as a Boc carbamate and the dihydropyridone moiety was oxidized to a pyridone with Pb(OAc)4. Pyridone 32 was prepared

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

• . This product arises from a Norrish–Yang cyclization/1,2-methyl migration cascade of 14 via intermediate 14a. Intriguingly, the substrate with R = H (14’) underwent only Norrish–Yang cyclization (95% yield) without 1,2-methyl migration [23]. It is hypothesized that the substituent at C9 in compound 14

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

• cascade to give enone 21 in 42% yield. Baeyer–Villiger oxidation of this highly activated alkene promoted an epoxidation/Baeyer–Villiger oxidation cascade to yield lactone 22 in 67% yield (dr 2:1). The low diastereoselectivity suggested that the epoxidation happened subsequent to the ring contraction, as

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

• radical initiated intramolecular cascade cyclization of 1,n-enynes to provide structurally diverse heterocycles (Scheme 4) [11]. Solvent selection dictated divergent reaction pathways under I2/TBHP oxidation. When an acetonitrile/water mixed solvent was used, iodine radical addition to the alkyne

• and co-workers achieved an innovative gold-catalyzed cascade cycloisomerization of 3-allyloxy-1,6-diynes to access cyclopropane- and cyclobutane-fused benzofurans/chromanols (Scheme 5) [12]. In this study, solvent polarity and trace water were identified as key parameters governing the reaction

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

• for synthesizing non-symmetric azobenzenes via a Pd-catalyzed cascade involving C–N coupling of arylhydrazines with aryl bromides, followed by oxidative dehydrogenation (Figure 1c). As our study was nearing completion, Váňa and co-workers disclosed a related Buchwald–Hartwig approach employing the Pd

• . Finally, di-ortho-substituted azobenzene 5d was also successfully prepared using this approach, achieving an excellent yield of 80%. The mechanism of the reaction was further outlined to explain the formation of all identified main and side-products (Figure 2). A two-step cascade Pd-catalyzed reaction is

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

• benzamides with terminal alkynes, 5-exo-dig aza-cyclization of 2-alkynylbenzamides as well as reductive cascade annulation of o-alkynylbenzamides. Pyrroles and imidazoles were formed efficiently via electrochemical annulation of alkynes with enamides and tandem Michael addition/azidation/cyclization of

• sustainable strategy for the preparation of 3-selenylindoles. In 2023, Satyanarayana also described a similar electrochemical cascade approach towards 3-selenylindoles from 2-alkynylanilines (Scheme 6) [202]. When graphite was used as anode, platinum as cathode and LiClO4 as electrolyte, the electrochemical

• obtained by electrochemical reductive cascade annulation of o-alkynylbenzamide (Scheme 10) [212]. Under 10 mA constant current with two platinum plate as electrodes and n-Bu4NPF6 as electrolyte, the reductive cascade cyclization of o-alkynylbenzamide 27 proceeded smoothly in the presence of N,N

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

• synthesis of amines by replacing the current toxic pathway based on ethylene oxide and dichloroethane [29]. Due to the high reactivity of α-hydroxycarbonyls, the main issue in this reductive amination reaction [30] was to control the cascade of consecutive and parallel reactions. The use of methanol as

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• synthesis of (–)-isochaetominine A was increased from 25.4% to 30.8% over five steps. Secondly, a new protocol featuring the use of an aged solution of K2CO3/MeOH to quench the DMDO epoxidation-triggered cascade reaction was developed, which allowed the in situ selective mono- or double epimerization at C11

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• assembly of a complex natural product with a three-dimensional framework in a cascade way. Later, this was regarded as an artificial mimic in laboratory of the biochemical transformations in nature. In the 20th century, Woodward elevated the field of natural product total synthesis to the artistic status

• reported. A bioinspired approach represents many advantages to bring benefits to total synthesis. It could rapidly achieve complexity of the target molecule from a much simpler precursor in diverse forms of transformations such as cascade reaction, cycloaddition, and C–H functionalization, thereby, shorten

• gymnothespirolignan A in excellent yield and good diastereoselectivity [38] (Scheme 6c). The minor epimer is gymnothespirolignan C, another natural product of this family. This cascade reaction supports the proposed biogenetic pathway of the newly isolated novel siprocyclic gymnothelignans. The bioinspired double

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

• 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

• propargylsilane 7d halogenation–cyclization cascade and Suzuki–Miyaura cross-coupling in the second step [22]. Thus, we have developed a faster and palladium-free route towards tetrahydrofurans 8. The latter can still be modified further through silicon–halide exchange followed by cross-coupling chemistry as

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

• , and Et3N in MeCN, the intramolecular Heck/hemiamination cascade reaction of 198 delivered the 5-exo cyclization product 199, simultaneously constructing the fused D and E rings in a single transformation. Three additional steps converted 199 to hydroxy ketone 200, which underwent SmI2-mediated

• , compound 266 was prepared in a seven-step sequence. Then, the cascade cyclization was accomplished by treatment with NaOMe in MeOH, followed by H2O, affording compound 267 in excellent yield and diastereoselectivity. A subsequent three-step sequence gave diol 268. Under DDQ and AcOH conditions, the

• diastereoselectivity. Compound 288 was then treated with Co(acac)2, 1,1,3,3-tetramethyldisiloxane (TMDSO), and O2 in degassed iPrOH, undergoing a hydrogen-atom-transfer (HAT)-initiated redox radical cascade to give pentacyclic alcohol 289, which was converted to C18/19 diol 290 in two steps. To differentiate the two

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem

• condensation, cyclisation, and cycloaddition as an efficient strategy for the rapid formation of complex spirocyclic products that could have value for the formation of novel, bioactive oxindoles. Keywords: cascade; cycloaddition; oxindole; spirocycle; stereochemistry; Introduction The Alstonia alkaloids are

• aldehyde 4 could now be tested in the cascade chemistry. This entails the addition of hydroxylamine to form the oxime, followed by cyclisation (with displacement of the tosylate) to give the nitrone for the desired dipolar cycloaddition reaction. Related chemistry (without the oxindole) with a halide

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• benzamides from isonitriles as well as in multicomponent reactions with isonitriles in general. Only a few examples of photochemical cascade arylation–cyclizations of isonitriles with diaryliodonium salts have been published [31][32][33]. To bridge this gap, we propose a photoredox-mediated strategy for the

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

• and colleagues published a one-step synthesis of spirooxindole 2,2-disubstituted oxetanes 11 via an unprecedented addition/substitution cascade (Scheme 4) [39]. The protocol reacts readily available 3-hydroxyindolinones 9 with phenyl vinyl selenone (10) in aqueous KOH at room temperature and gives

• performing the reaction under visible light irradiation, or coupling the reaction to other light-induced processes to produce new classes of products. In 2018, Aitken and co-workers reported a synthesis of previously unknown tricyclic 4:4:4 oxetanes 73 through a photochemical triple cascade reaction starting

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

• synthetic strategy. The tandem Suzuki coupling/Knoevenagel condensation strategy leading to PAH 85 was independently reported by Liu [61] and Mastalerz (Scheme 12) [62]. The first group reported a cascade formal [3 + 4] annulation between triple boronic ester 83 and naphthalene 84 which combines a Suzuki

• 660 nm. Würthner and co-workers developed a cascade [3 + 3] annulation strategy, where Suzuki cross-coupling is followed by C–H arylation, and applied it to various electron-deficient nanographenes [81][82][83][84]. This strategy can also be applied to non-alternant PAHs. For example, azulene 127

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

• transformations, (4) electrochemical approaches, and (5) metal-free or electron donor–acceptor (EDA)-driven systems. The substrate scope, limitations, and mechanistic aspects of these radical cascade cyclization strategies are critically examined. Review N-Arylalkenes: alkyl C(sp3)–H radicals Early investigations

• activated alkenes involving benzylic C(sp3)–H bonds through a cascade cyclization process (Scheme 1) [2]. This organomediated approach can be facilitated by a catalytic amount of Lewis acid. Using DTBP as the oxidant and IrCl3 as the promoter, a range of benzylic C–H bonds in arylmethanes

• oxidant and initiator, enabling an efficient intermolecular cascade cyclization process (Scheme 5) [5]. In this strategy, a novel, selective, metal-free synthetic method was introduced for the synthesis of isoxazoline-featured oxindoles through iminoxyl radical-promoted cascade oxyalkylation

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• . Reproduced from [52], Resources, Conservation and Recycling, vol. 193, by D. Fang; F. Bi; L. Yang; W. Hu; Z. Hua; H. Wei; C. Chen; Y. Tu; P. Shao; M. Li; X. Luo; G. Yang, “Selective extraction of gold from strong acid e-waste leachate through H+-triggered cascade reaction of thiolated β-cyclodextrin

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• other hand, Fan and co-workers (2020) prepared α-amidoketone 71 by employing vinyl azide and cinnamic acid (7) in good yield via cascade reaction (Scheme 23B) [58]. The thermal decomposition of the azide led to the generation of the reactive azirine intermediate 72. Moreover, Li and co-workers (2020

• ) employed N-formylpyrrolidine (FPyr) and trichlorotriazine (TCT) to catalyze the amidation of cinnamic acid derivative 121. The reaction proceeds via formation of the reactive acid chloride 36 through cascade reaction involving reactive intermediates 123 and 124 (Scheme 37) [72]. Zeng and co-workers (2019

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• nucleophilic addition or substitution, the resulting iminium ions often undergo direct hydrolysis, preventing further use in a cascade nucleophilic addition. As a result, enamines are not ideal partners in tandem reactions for the synthesis of nitrogen-containing products. As analogues to enamines, the

• , despite the potential for such a tandem reaction to provide a more efficient route to these complex structures. In 2016, Wang and co-workers indigenously designed and developed a cyclization/Pictet–Spengler reaction cascade, leveraging the nucleophilicity of the tertiary enamides and the electrophilicity