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

• southern furan moiety of 69. Finally, hydrolysis of the carbonate followed by oxidation of the resulting diol completed the Norrish–Yang cyclization precursor gracilisoid A (49). Irradiation of 49 under anaerobic conditions with a CFL, followed by treatment with silica gel, successfully generated a pair of

• separable regioisomers: gracilisoid F (54) in 42% yield and gracilisoid H (56) in 40% yield, respectively (Scheme 8). Here, light triggered a regiodivergent Norrish–Yang cyclization, while the acidic nature of silica gel sufficiently promoted an α-hydroxy ketone rearrangement. This type of rearrangement was

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

• activated ynamide. This sequence resulted in the formation of spiroindoleninium intermediate 130 (Scheme 27, path a). Subsequent intramolecular Mannich cyclization proceeded, yielding the 1H-pyrrolo[2,3-d]carbazole derivatives 131. When silica gel was utilized as the catalytic medium, the same Michael

• addition happened to generate the spiroindoleninium intermediate. This transient species was subsequently trapped by water physisorbed in the silica gel, forming hemiaminal adduct 132. A 1,5-hydride shift was then mediated by Al2O3, ultimately affording the spiro[indoline-3,3'-pyrrolidin]-2-one derivatives

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• spectrometer equipped with a Direct Insertion Probe (EI+ ionization) or on a Bruker Q-TOF Maxis Impact mass spectrometer (ESI+ ionization) coupled with a Waters Acquity I-Class UPLC system equipped with a diode array detector. The reactions were followed by analytical thin-layer chromatography on silica gel 60

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• structure analysis was performed on a Bruker SMART diffractometer equipped with a CCD area detector at 120 K. Silica gel 60 F254 precoated plates on glass from Merck Ltd. were used for thin-layer chromatography (TLC). General procedure for the synthesis of conjugates 2a–h (S)-2-[2,10-Bis(4-methoxyphenyl

• of Celite, and then evaporated to dryness. The crude product was purified by column chromatography on silica gel (EtOAc) to yield amine (S)-2a (203 mg, 83% yield) as colorless solid: mp 164.2–165.5 °C; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 1.8 Hz, 2H), 7.62–7.56 (m, 6H), 7.44 (d, J = 7.8 Hz, 2H

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

• mixture was evaporated to remove MeOH solvent and the residue was redissolved in MeCN (2 mL) and heated at 130 °C for 2 h in a sealed vial. After the reaction had reached completion as monitored by TLC, the reaction mixture was concentrated in vacuo. Column chromatography on silica gel afforded products

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

• bicyclic alkanes, used as fuel additives, by hydrodeoxygenation catalyzed by iridium/rhenium oxide supported on silica [182]. Conversion of furfural to amines: The synthesis of m-xylylenediamine from furfural and acrylonitrile through a Diels–Alder/aromatization sequence was developed by Wischet and Jérôme

• 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

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

• was then treated with AcOH to afford the putative iminium cation to be chemoselectively reduced with NaBH3CN to ultimately reach the amine functionality. Through this protocol, the amine product was obtained, but it could not be isolated from silica gel for its high polarity. Thus, the extracted crude

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• CH2Cl2 (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The reaction crude was purified by flash column chromatography on silica gel (n-hexane/ethyl acetate 8:2) to give the desired pure product. General procedure for in-flow electrochemical imino

• purified through flash column chromatography on silica gel to give the isolated pure product. X-ray determined structure of chiral piperazine 2b. Synthesis of vicinal diamines via imino-pinacol coupling in the presence of metal-based reductants. Light-promoted imino-pinacol coupling for the synthesis of

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

• chromatography on silica gel. The structure of this isomer could not be ascertained with certainty from NOESY analysis and initial crystallisation attempts were unsuccessful. However, through use of encapsulated nanodroplet crystallisation (ENaCt), a high-throughput crystallisation technique which controls the

• silica gel 60F254 plates and visualised by UV irradiation at 254 nm or by staining with an alkaline KMnO4 dip. Flash column chromatography was performed using silica gel (40–63 micron mesh). Infrared spectra were recorded on a Perkin Elmer Spectrum RX Fourier Transform–IR System and only selected peaks

• ), dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/petrol 1:2, to give the alcohol 2 (824 mg, 30%) as an amorphous solid; data as reported [30]. Et3N (1.5 mL, 10.8 mmol) was added to the alcohol 2 (782 mg, 3.6 mmol), TsCl (1.03 g

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• functional groups are isolated together in confined space [7][8][9]. In the solid state, the generation of such multifunctional cavities has been pursued upon nanoporous scaffolds that include polymers of intrinsic microporosity (PIMs) [10][11][12][13], mesoporous silica materials (MSMs) [14][15][16][17

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• -linking of polymers (such as PLGA and PEG), inorganic materials (such as gold and silica), or biomolecules (lipids and proteins), enabling efficient drug loading and controlled release [66][67][68]. Among them, amphiphilic CAs that incorporate both hydrophilic groups and hydrophobic alkyl chains through

• hybridized with various inorganic materials, such as metal-organic frameworks (MOFs), mesoporous silica nanoparticles (MSNs), metal nanoparticles, and carbon materials [87]. By designing through electrostatic and non-covalent interactions, PAs can be used as "molecular switches" to construct mechanized MOFs

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• , ON, Canada). Reactions were monitored using thin-layer chromatography on aluminium-backed silica plates (Sigma-Aldrich) using either UV-light (254 nm), iodine, KMnO4, phosphomolybdic acid, or p-anisaldehyde for visualization. Tetrahydrofuran (THF) was dried and distilled over sodium/benzophenone

• ), and brine (100 mL). After drying over anhydrous MgSO4, the solvent was removed in vacuo and the crude product was purified by flash chromatography on silica gel (EtOAc/hexane; gradient 1:10 → 1:2) to give 21 as a colorless solid (6.7 g, 80%, 2 steps); Rf = 0.5 (EtOAc/hexane 1:2); mp 50–52 °C (lit. mp

• with EtOAc (3 × 50 mL) and the combined organic layers were washed with water (100 mL) and brine (100 mL), and then dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (EtOAc/hexane gradient 1:10 → 1:1, 1% AcOH

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• . tuberculosis [121]. The TMS-glycosides were prepared from the corresponding hemiacetals by acid-catalyzed silylation, involving a silica gel-promoted in situ anomerization of the O-TMS-β-glycoside to its more thermodynamically stable α-counterpart [121]. This protocol enabled the efficient synthesis of TMS

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• standard. Analytical thin-layer chromatography (TLC) was performed with silica gel 60 Merck F254 plates. Column chromatography was performed with silica gel 60N (spherical neutral). Recyclable preparative high-performance liquid chromatography (HPLC) was carried out on a Japan Analytical Industry Model

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• hybrid decamer 3 in a previous report [26], via a Suzuki–Miyaura cross-coupling reaction between dibromo precursor 1 and borylated precursor 2 (Scheme 1). The resulting mixture was successfully separated by column chromatography on silica using CH2Cl2/n-hexane as an eluent to give icosamer 4 in 6% yield

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• chromatography on silica gel using DCM as eluent. Design and synthetic strategies for the target hydantoin/1,2,4-oxadiazoline spiro-compounds. Atropoisomerism of ortho-substituted spiro-compounds 5b and 5d. Cytotoxicity investigation of hydantoin/1,2,4-oxadiazolines 5 (MTT test, HCT116 cell line) and selected

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• Commercial chemicals and solvents were used as received. If not stated otherwise, products were purified by filtration through short silica gel plugs (200–400 mesh) by using freshly distilled solvents as eluents or by recrystallization. Melting points were determined in capillaries with an Aldrich Melt-Temp

• evaporated, and the residue was analyzed by 1H NMR. Depending on the composition of the crude product, this material was either separated by preparative layer chromatography on the plates coated with silica gel (CH2Cl2 as the mobile phase) (separation of 9h and 10h) or crystallized from hexane/CH2Cl2 mixture

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

• harness their Lewis-acidic and weakly oxidizing properties, respectively. In addition, microwave irradiation increases the reaction rate considerably. Furthermore, the use of a solid Cu(I) catalyst immobilized on an aminated silica support allows for a heterogeneous and cost-effective process, featuring

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

• supported copper(II) catalysts on covalently modified silica [51][52], we have set out to develop a new heterogeneous catalyst with atomically distributed active sites for the mild and efficient C–H amination of benzoxazole. This approach was chosen because the silica derivatisation and copper deposition

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• foundation, the same group in 2024 developed a series of structurally refined aza[7]helicenes (compounds 12a and 12b) under modified Scholl reaction conditions [25]. These products were obtained as optically active diastereomers, which were successfully separated using silica gel chromatography. Additionally

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• Fluorochem and used as received. The solvents used for the experimental synthesis (HPLC grade) were purchased from Sigma-Aldrich. All other materials were commercial products of analytical grade and used as supplied. Analytical TLC (thin-layer chromatography) was performed on Merck silica gel 60 F254

• on silica gel, using dichloromethane/ethyl acetate 6:1 as eluent to obtain the pure product as bright orange solid (0.31 g, 62% yield). 1H NMR (500 MHz, CDCl3) δ 8.93 (dd, J = 1.2 Hz, 4.6 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 9.5 Hz, 1H), 7.49 (t, J = 8.0 Hz, 2H

• formed, was washed with water several times and dried. The crude material was purified by column chromatography on silica gel, eluting with dichloromethane. Evaporation of the solvent afforded the pure target compound as orange solid (0.26 g, 38% yield). 1H NMR (500 MHz, DMSO-d6) δ 14.7 (br s, 1H), 8.90

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• solution was stirred for 10 min in an ice bath, then iodonium salt 2a or 2f (1.5–2.0 equiv) was added in one portion. The reaction vessel was removed from the ice bath and the reaction mass was stirred for 6–60 min, then transferred to a silica gel column and the corresponding 2-sulfonyl-2,3-dihydro-1,2

• (1.5 mL) was added dropwise. The reaction vessel was removed from the ice bath and the reaction mass was stirred for 10–30 min, then transferred to a silica gel column and the corresponding 2-sulfonyl-1,3-thiazole 3 was isolated. X-ray structure determination of 3aa. Crystal data for C21H21N3O3S2 (M

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• in Table 1. The yield of compounds 1 after flash chromatography on silica gel under modified conditions (B) are significantly higher than under standard conditions (A). The results demonstrate the broad applicability of the optimized reaction conditions. Acid chlorides with electron-withdrawing (-CN

• ® and purified by flash chromatography on silica gel (n-hexane/acetone 3:1). Then, the crude product was suspended in n-hexane, the supernatant separated by filtration and the precipitate was dried under vacuum to afford aroyl-S,N-ketene acetal 1i (1.78 g, 4.93 mmol, 99%) as a yellow solid. Mp 159 °C

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

• chromatography on silica gel. Recent approaches for the synthesis of β-ketophosphonates by the oxyphosphorylation of unsaturated compounds. The scope of the discovered copper(II)-mediated phosphorylation of enol acetates. Gram-scale synthesis of 3a. Control experiments. Proposed mechanism for copper(II) mediated

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• chromatography on silica gel because of their low polarity and poor solubility in n-hexane. On the other hand, nitration of [3.3.3] gave solely the six-fold nitrated product due to low solubility of the starting material [46]. The current reaction is the first practical method for the selective