Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• obtained in general procedure B was dissolved in dichloromethane and cooled to 0 °C under argon atmosphere. Then, triphenylphosphine and carbon tetrabromide were added and stirred at room temperature for two hours. Afterwards, the entire mixture was loaded on a silica gel column and eluted with 100

• % dichloromethane. General procedure D. In a manner similar to [11], the product obtained in general procedure B, methanesulfonyl chloride, and triethylamine were dissolved in dichloromethane and stirred overnight at room temperature. After reaction control and 100% consumption of the starting material, the entire

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• temperature overnight. Afterwards, the mixture was centrifuged (4400 rpm, 10 min) to pellet excess insoluble C1. An aliquot of the supernatant and a solution of dimethyl malonic acid as a non-binding internal standard of known concentration were transferred to an NMR tube followed by collection of a 1H NMR

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• -branched amino acids. Results and Discussion Aromatic amino acids First, we concentrated our efforts on synthesizing the aromatic, fluorinated amino acids (Scheme 2). The corresponding alkyl bromide precursors were commercially available. We screened a broad range of reaction conditions such as temperature

• identified as optimal delivering a yield of alkylated complex of 60% (Table 1, entry 4). With DBU as base different solvents differing in polarity have been tested. At room temperature, acetonitrile proved best and increased the yield to 88% (Table 1, entry 11). Lowering the temperature to 0 °C led to a

• (II) complex of bisTfMePhe have differed significantly. Here, sodium hydride (NaH) was identified as optimal base leading to a yield of 85% when using DMF as solvent at 0 °C to room temperature (Table 2, entry 4). Testing different base equivalents, solvents, solvent mixtures and temperatures didn’t

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

• synthesis underscore the robustness and reliability of this copper-mediated transformation in creating stereochemically complex molecules. Mechanistic investigations revealed several key factors controlling the stereochemical outcome of these transformations. The extremely low temperature (−100 °C) during

• temperature led to a significant decrease in dr values, suggesting partial racemization. This observation highlights the importance of careful experimental handling of [RCu·ZnX2·L] species {X = Br, Cl; L = P(OEt)3}, where both temperature control and reaction time must be precisely managed to maintain

• optimization revealed LiOt-Bu and diphenyl phosphate as the optimal metal alkoxide and leaving group, delivering the desired product 32 in high yield and high enantioselectivity at room temperature with only 2 mol % catalyst loading. The scope of this transformation proved to be remarkably broad. In addition

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• conditions at room temperature, and 2.0 F charge (if not otherwise noticed) with current density of 12 mA/cm2 was passed through the colorless reaction solution. The resulting clear, colorless (sometimes pale yellow) solution was concentrated under reduced pressure and the crude product was purified by

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• for the types of reactions that can be used for the elaboration of ADCs. Among the signature features of photochemical, single-electron transformations is their ability to be conducted in dilute aqueous media at room temperature and at neutral pH [47]. Additionally, the distinctive mechanistic

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• Anton Paar MCP-150 Polarimeter with sodium D line at 589 nm and 100 mm path length. HRESIMS mass spectra were measured with a maXis ESI TOF mass spectrometer (Bruker Daltonics) [scan range m/z 100–2500, rate 2 Hz, capillary voltage 4500 V, dry temperature 200 °C], coupled to an Agilent 1200 series HPLC

• ), solvent A: H2O + 0.1% formic acid; solvent B: acetonitrile (ACN) + 0.1% formic acid, gradient: 5% B for 0.5 min, increasing to 100% B in 20 min, maintaining isocratic conditions at 100% B for 10 min, flow = 0.6 mL/min, UV–vis detection 190–600 nm]. Preparative HPLC was achieved at room temperature on an

• mixture was stirred at room temperature overnight. The reaction mixture was suspended in water (25 mL) and extracted with CH2Cl2 (2 × 25 mL). The combined organic layer was evaporated to dryness to give a residue, which was dissolved in methanol (300 μL) and purified by preparative HPLC [ChemStation

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

• , successfully forming the aryl-containing quaternary center. However, in this step, the reaction was too rapid to control. After optimizing the reaction time and temperature, the reaction was carried out at −30 °C for 15 minutes and product 14 was isolated in a yield as high as 58% [14]. Iodination of compound

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

• was carried out via copper catalysis or iodine–acid catalysis. Interestingly, when aliphatic amines are employed (R3 = n-Pr, n-Bu, product 8) only the N atoms are incorporated in the structure of the final product, probably because the high temperature favors the elimination of the alkyl group. The

• the most used one. This is usually done at a load of 5 mol % in CH3CN as solvent and CH2Cl2 as a C1 synthon, under moderate reaction conditions (60 °C). Consequently, this synthetic strategy is less dependent on temperature compared to AAA coupling [62]. Several reports also showed that gold (as AuCl3

• , 5 mol %) [63], indium (as In2O3 nanoparticles, 5 mol %) [64], iron (as FeCl3, 20 mol %) [65], cobalt (as CoBr2, 10 mol %) [66], and nickel (as Ni(py)4Cl2, 15 mol %) [67] can act as metal catalyst for the 3CC reaction. In all these cases, the temperature was lower (usually between 60–80 °C) compared

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• chiral halonium salt. Next, the reaction temperature was optimized, and −40 °C was found to be optimal (Table 1, entries 7–9). Further optimization of the reaction conditions (amounts of potassium carbonate and pre-nucleophile, catalyst loading, and concentration) were conducted, and the reaction with

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• (Table 1). First, we tried several solvents (dichloromethane, toluene and dichloroethane, entries 1–3 in Table 1) at room temperature, obtaining product 5aaa in yields around 50% with high diastereoselectivity (up to 6:1) after several days. Increasing the temperature to 50 °C (Table 1, entries 4 and 5

• diastereoselectivity after 24 h of reaction (61% yield and 7:1 dr, Table 1, entry 14). By lowering the reaction temperature to 50 °C using the same catalyst (Table 1, entry 15), the yield of the reaction increased slightly to 73% in 24 hours. Disappointingly, the bifunctional thiourea THIO-1 gave a lower yield and

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• Abstract A new deep-blue emitting and highly fluorescent anthracene (ANTH) derivative containing perfluorobenzyl (BnF) groups, 9,10-ANTH(BnF)2, was synthesized in a single step reaction of ANTH or ANTH(Br)2 with BnFI, using either a high-temperature Cu-/Na2S2O3-promoted reaction or via a room-temperature

• ampules and with PERY using solution-phase reactions at elevated temperatures in the presence of Cu metal or another reducing agent [22]. In this study we first explored the approaches from our previous work: a high-temperature gas-phase reaction between ANTH and BnFI [18][19], and a solution-phase

• were shown to form from ANTH(RF)n derivatives within minutes at room temperature in the presence of oxygen when irradiated with a high pressure mercury lamp [32]. When 9,10-bis(perfluorooctyl)anthracene was dissolved in CHCl3 and irradiated for 350 minutes, photodecomposition was observed. However, the

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• included two additional bimane samples, Me2B and Me4B. These samples were crystallized from a MeOH–DCM 1:1 (v/v) mixture which was left to slowly evaporate over the course of several days at room temperature, followed by single-crystal X-ray diffraction to determine their structure (Figure 4) and crystal

• )bimane (DMOCDO10) and syn-(Me,Me)bimane (DXABIM10) [26], a room temperature structure of Me4B (TNZBCO10) [27], and a planar syn-(H,ethynyl)bimane (WAYHEJ) [28]. Optical properties The optical properties of the three bimanes were measured to investigate differences in their excited state properties, as

• 1:1 (v/v) solution which was left to evaporate at room temperature over the course of a few days. Photophysical properties Fluorescence spectra were measured on a Horiba FluoroMax Plus spectrofluorimeter. UV–vis spectra were measured on a Shimadzu UV-1900i UV–vis spectrophotometer. Absorption and

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• methanol (1.3 mL). Anhydrous magnesium sulfate (340 mg, 2.82 mmol, 10 equiv) and the respective amino alcohol (2.82 mmol, 10 equiv) were added. The mixture was sonicated for 30 minutes and subsequently stirred at room temperature for 16 h. After cooling to 0 °C, sodium borohydride (96.1 mg, 2.54 mmol, 9

• equiv) was added in portions over the course of 1 h. The mixture was stirred for additional 2.5 h at room temperature. Afterwards, the volatiles were removed under reduced pressure and the residue was taken up in dilute aqueous acid (for composition see individual experiments in Supporting Information

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting

• ] using 20 mol % of catalyst A and 20 mol % of p-nitrobenzoic acid (PNBA) as co-catalyst in different solvents at room temperature. The results obtained are summarized in Scheme 3 and Table 1. The progress of the reaction was monitored using thin-layer chromatography (TLC) and 1H NMR analysis of the

• provide the highest enantiomeric ratio. The influence of catalyst, co-catalyst, and temperature on the reaction progress and enantioselectivity was further investigated. Different essays using 0.028 M toluene solutions were carried out, and the results are summarized in Table 2. The reaction also occurs

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• Na2CO3 was ground in a mortar at room temperature for 3–5 min. Second, the reaction mixture was transferred into a quartz tube, heated to 50 °C (heating mantle) for 18 h, while being irradiated with blue LEDs under air-equilibrated conditions. In these conditions, product 3.3 was isolated in excellent

• optimal temperature regulation using a fan. To overcome the challenge posed by the non-transparency of milling jars, a glass capsule was utilized. Teflon balls were employed to grind the reagents, thereby minimizing wear on the milling vessel. As a benchmark reaction, they selected the photochemical

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• required thermal decomposition of the diazonium salt to effect the cyclization. In the quest for mild (room temperature) and scalable conditions toward cyclic diaryl λ3-bromanes 1 we realized that bromanyl units possess leaving group abilities comparable to the diazonium moiety [1][15]. Hence, the

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• organic cages allows structural analysis in a way not possible for assemblies [38][39][41][42][43][44]. Due to their enhanced stability over imine assemblies, our amide-linked cages are amenable to complex processing (the cages remain unchanged in connectivity across changing solvents and temperature) and

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• temperature or the activation entropy, hydrogen bonding, solvent [24], nature of the leaving groups and the promoter used [25]. The mechanism of glycosylation reactions has long been categorised mostly as dissociative SN1 reactions proceeding through stabilised oxocarbenium ions with the role of counterions

• room temperature was the only difference with the pivaloyl group. Protecting the C-2 hydroxy group as ADMB ester yielded 1,2-trans glycosides in high yields. However, its participating mechanism is still unclear. So, we reserve our views on placing the use of ADMB as potential neighbouring group

• species was confirmed by low temperature NMR spectroscopy. Similarly, Ito et al. also introduced the concept of using 2-O-(o-tosylamido)benzyl (TAB)-modified donor 103 for the stereocontrolled synthesis of both 1,2-cis and 1,2-trans glycosides under modified reaction conditions [154][155]. They

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• temperature (23 °C). Chromatography was carried out on columns filled with Al2O3 of II–III degree of activity according to Brockmann. Melting points were determined on a Fisher-Johns melting point apparatus. 1,1,2-Trimethyl-1H-benzo[e]indolenine (2a, 98%, Alfa Aesar), 2,3,3-trimethyl-3H-benzo[g]indolenine (2b

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -nitroacrylates 1a,b with 2-hydroxynaphthalene-1,4-dione (2a). The reaction proceeds successfully in a methanol solution in the presence of AcOK for 3 h at room temperature, resulting in the formation of a mixture of alkyl 4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxylate 3a,b and alkyl 4,5-dioxo-4,5

• -c]chromene-3-carboxylates 5a,b with a yield of 84–85% were obtained under the same conditions as a result of the interaction of bromonitroacrylates 1a,b with 4-hydroxy-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5(6H)-dione (2b) (ratio acrylate/CH-acid/AcOK = 1:1:1.5, room temperature, 1 h) (Scheme 5

• Shimadzu UV-2401 PC spectrometer for samples in DMSO solutions in fused quartz cuvettes (optical path length 1.01 mm). Luminescence excitation spectra and luminescence spectra were recorded on a Shimadzu SF-6000 spectrofluorimeter in a 1 cm thick quartz cuvette at room temperature in a DMSO solution (c

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• mm, were inoculated with rice in 10 × 1 L Erlenmeyer flasks, each containing 180 g of rice and 180 mL of distilled water that were foremost autoclaved, and the mixture was incubated for 16 days under static conditions at room temperature until full mycelial growth was achieved. Upon reaching optimal

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• was found that the reaction did not proceed in DMF as solvent (Table 1). When the reaction was carried out in dichloromethane, dichloroethane, acetonitrile, and toluene, the expected product 3a was produced in low yields (entries 2–5 in Table 1). The reaction in toluene at elevated temperature

• resulted in a slight increase of the yield (entries 6 and 7 in Table 1). In the presence of 20 mol % of DMAP, the reaction in toluene at room temperature afforded the product 3a in 72% yield. However, increasing the amount of DMAP decreased the yield (entries 8–10 in Table 1). Additionally, stronger bases

• such as DABCO, DBU, triethylamine, and K2CO3 also resulted in the significant reduction of the yields. Therefore, the reaction of MBH nitrile of isatins and arylamines can be simply carried out in toluene at room temperature in the presence of a catalytic amount of DMAP. With the optimized reaction

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• , Me: methyl). Cyclic voltammograms of 1 and 2. UV–vis–NIR electronic absorption spectra of 1 (top) and 2 (bottom) during the electrochemical oxidation in 0.1 M n-Bu4N·PF6 in CH2Cl2 at room temperature. The traces are black lines for neutral, blue lines for radical cation, and red lines for dication

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• generate crotonic condensation adducts of active methylene compounds and formaldehyde at room temperature in the absence of strong acids and bases. The formed adducts were highly reactive intermediates capable of reacting with dienes in a three-component reaction, leading to the formation of Diels–Alder

• –Alder products were isolated from the reaction mixtures. In the present study, we carried out similar three-component reactions under significantly milder conditions (room temperature), and the main or only [4 + 2]-cycloaddition products in most cases were carbocyclic ones. Results and Discussion

• in a high yield in the presence of ʟ-proline could be explained by the efficient crotonic condensation of formaldehyde and acetylacetone (1), followed by the addition of the second equivalent of diketone 1 to the highly reactive methylidene intermediate. The mild reaction conditions (room temperature