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

• alcohols 13 and a binary Al/TBAB catalyst (Scheme 5) [40]. The reaction is carried out in toluene upon mild heating, providing the bicyclic products in high to excellent yields. Both electron-rich and electron-poor phenyls as well as aliphatic chains worked well, however, increased temperature and catalyst

• chlorides (Scheme 11a) [44]. The authors found that the secondary alcohol precursors were less reactive and that best results were obtained at low temperature (≤−50 °C) and in chlorinated solvents. The synthesis of these cages was later revisited by Le Drian et al. in 2011 who studied a Lewis acid-catalysed

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• and operational scalability [9][10]. Moreover, a high temperature and additive oxidants are generally required, which would limit the substrate scope. The hydrogen atom transfer (HAT) process has emerged as a powerful avenue for addressing these challenges, leveraging the HAT reagents to selectively

• radical from N–S bond cleavage The work of Alexanian’s group has significantly advanced the field of organic synthesis over recent years, particularly in the area of N–S bond homolytic cleavage [92][93][94]. Initial studies demonstrated that high-temperature conditions were required to facilitate this

• ambient temperature and visible-light irradiation, achieving site-selective bromination (products 94–96) in 51–99% yields across electronically differentiated positions. The system's operational mildness and functional group tolerance highlight its suitability for late-stage functionalization of complex

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

• ], TPH-graphene (Figure 2b) [23], PHH-graphene [24] and ψ-graphene [25]. Notably, fragments phagraphene and TPH-graphene have already been synthesized via on-surface chemistry and characterized using low-temperature scanning probe microscopy with CO-functionalized tips [23]. These non-alternant carbon

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

• temperature, and solvents. The optimal conditions were identified as using 10 mol % Sc(OTf)3 and 2 equivalents of Ag2O at 120 °C under an argon atmosphere. The substrate scope was then evaluated using various o-alkynylarylacrylamides and alkyl nitriles under the optimized reaction conditions. Substrates with

• amount of Bu4NPF6 as the supporting electrolyte in a MeOH/TFE 11:1 (v/v) co-solvent mixture under blue LED irradiation at a constant current of 1.5 mA for 12 hours at room temperature. A wide range of substrates exhibited good functional group tolerance, with 3-homoallylquinazolin-4-ones bearing electron

• particularly noteworthy for its use at room temperature, requiring no transition metals, photocatalysts, or additives. Notably, Umemoto's reagent served as the trifluoromethyl source, and the reaction was facilitated under blue LED irradiation, achieving good to excellent yields. Moreover, this approach

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

• -N-benzylbenzothiazolium salts in 1,4-dioxane at room temperature in short reaction time in 20–99% yield. This protocol represents a considerable improvement over the standard synthesis in 1,4-dioxane/ethanol mixtures at elevated temperatures. Keywords: aroyl chlorides; aroyl-S,N-ketene acetals

• examples), the average yield of 57% indicates that the process might require optimization, in particular, for further methodological implementation. Here, we report on the improved synthesis of (hetero)aroyl-S,N-ketene acetals 8 by careful solvent and temperature optimization. Results and Discussion The

• from in the process. For suppressing the formation of side products by self-condensation of S,N-ketene acetal intermediates the reaction temperature has to be kept as low as possible for assuring kinetic control. Therefore, in contrast to the standard protocol [5][6] (Scheme 2), reacting aroyl

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

• the desired product only in trace amounts (Table 1, entry 3). The optimal loading of the catalyst was examined (Table 1, entry 4); the best results were obtained with 20 mol % of copper sulfate, slightly lower yield (64%) was observed with 10 mol % loading of the catalyst. Increased temperature was

• – 4500 V); mass range from m/z 50 to m/z 3000 Da; external calibration with Electrospray Calibrant Solution (Fluka). A syringe injection was used for all acetonitrile solutions (flow rate 3 μL/min). Nitrogen was applied as a dry gas; interface temperature was set at 180 °C. General reaction conditions

• stirred for 3 hours at 70 °C under air (air condenser) and then cooled to room temperature, and rotary-evaporated under reduced pressure. An additional evaporation step using a rotary vane pump (0.5 mmHg) at 80 °C was made for the evaporation of phosphite excess. The residue was isolated by column

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

• ) [55][56][63][64][65][66] yielded the monoformyl product [4.3.3]_CHO, in a selective manner (Table 1, entry 1). To suppress decomposition in the overnight reaction at room temperature, the reaction time was reduced to 1.5 h, which afforded [4.3.3]_CHO in an isolated yield of 80% (Table 1, entry 2). The

• reaction temperature and time. Indeed, bromination of [3.3.3] and [4.3.3] was reported as three/six- and two-fold reactions, respectively [45][47][53]. If the amount of bromine was limited, the resulting nearly random mixtures of brominated compounds would be practically impossible to separate by

• connections, but all of them displayed CO2 adsorption properties at 298 K probably due to the 3D components. The uptake values at standard temperature and pressure (STP) were 15–29 cm3·g−1 at 90 kPa. In this series, a sample with higher T90 and CY values tended to exhibit a higher adsorption capacity for CO2

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• rate constant of the reaction leading to the other regioisomer at the reaction temperature of 90 °C. Experimentally, it is observed that the regioselective C–H activation happens on the more electron-rich aromatic ring with the methoxy substituent as opposed to the one with the alkoxycarbonyl group

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• in 89–98% yields. Reactions of 4 with acryloyl chloride (5, 1.5 equiv) in the presence of Et3N (2 equiv) at room temperature in anhydrous CH2Cl2 for 6 h afforded 19 N-acylated compounds 6 in 80–90% yields [19]. With N-acylated GBB adducts 6 in hand, the synthesis of imidazopyridine-fused

• in 1,2-dichlorobenzene at 180 °C for 4 h, which gave 8a in 85% conversion and 82% isolated yield (Table 1, entry 3). Other solvents like toluene and xylene gave minimal or no product. Different combinations of temperature and reaction time couldn’t improve the yield. Among the various Lewis acids

• irradiation at 100 °C for 1 h (Scheme 2, Table S1 in Supporting Information File 1). Nineteen distinct adducts 4 were obtained in 89–98% yields. The reactions of GBB adducts 4 with acryloyl chloride (5, 1.5 equiv) in the presence of Et3N (2 equiv) at room temperature in anhydrous CH2Cl2 for 6 h afforded 19 N

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• °C and leaving it at the same temperature for an additional 15 minutes, two products, 47a and 47b, were formed. After desulfonylation with sodium amalgam (Na·Hg) in methanol and column chromatographic purification, the anticipated diols 48a and 48b were obtained in 72 and 11% yield, respectively. The

• presence of DCC and DMAP. The reaction was allowed to proceed for 6 h at room temperature, after which the temperature was reduced to −10 °C, and sodium borohydride was added. The mixture was left to react for 12 hours, yielding compound 53 in 96%. This intermediate was then converted to acrylic acid 54 by

• presence of pivaloyl chloride, triethylamine, and lithium chloride to produce compound 71 in 86% yield. Diastereoselective methylation of 71 was achieved by treating it with NaHMDS at low temperature, followed by the addition of methyl iodide, resulting in a diastereomeric ratio greater than 98:2

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• scaffold for aminations with 14 commercially available primary amines. Reacting scaffold 1 with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18–87%) and high purity (≥95%) following chromatography workup. The structures of the 14 previously

• ]triazolo[4,3-a]pyrazine (compound 1; Scheme 1) according to the approach previously described by Korsik et al. [10] was performed, but without reflux, in order to compare the yield obtained for the aminated product under our further modified conditions (neat phenethylamine only, room temperature; Scheme 1

• column chromatography (and additionally by HPLC for the toluene reaction), the reactions also gave comparable yields of compound 2 (70% for toluene/silica and 82% for only phenethylamine at room temperature). Only the tele-substituted product was observed in either reaction mixture, consistent with

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

• second-sphere coordination of [AuBr4]− and two α-CDs, accounts for the co-precipitation of α-CD·[Rb(OH2)6]+[AuBr4]− and α-CD·[Cs(OH2)6]+[AuBr4]−. Improvements of the method for the precipitation of gold in the form of {α-CD·[K(OH2)6]+[AuBr4]−}n were further investigated, namely the effect of temperature

• and ratio of α-CD that was added to the salt solution [40]. Studies at different temperature values demonstrated that the precipitate is less soluble as the temperature decreased and thus the gold extraction was optimal at 0 °C. Tests with excess stoichiometries of α-CD (2:1, 3:1, 4:1, 5:1) showed

• of precipitating gold from a solution even when it is found in low concentrations and the possibility of operating at ambient temperature. Lab-scale tests with e-waste recovery show promising extraction yields. Future developments will further optimize parameters and scale up the procedure

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• amount of water was added to activate the boronic species and to dissolve the inorganic base under otherwise inert conditions. The reaction mixture was then stirred at room temperature overnight. Under these conditions, a variety of boronic acids with different steric and electronic properties was

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• procedure [16]. General procedure for the synthesis of ethyl 2-(oxazol-2-yl)alkanoates 3 Sc(OTf)3 (9.8 mg, 0.02 mmol) was added in a dried 10 mL reaction tube, then it was heated to 220 °C and dried at 220 °C for 2 h under oil pump vacuum. After gradually cooling to room temperature, the chiral salen ligand

• with a syringe and the mixture was stirred at 55 °C for 24 h. After gradually cooling to room temperature and removal of the solvent under reduced pressure, the crude residue was purified by basic aluminum oxide column chromatography with petroleum ether/ethyl acetate 1:10 to 3:7 (v/v) as eluent to

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

• excellent yield (Scheme 2) [32]. The formed anhydride 3 was smoothly converted to the amide at room temperature. This method provides a green approach by allowing cinnamic acid derivatization in water as a benign solvent. Similarly, Rajendran and Rajan (2023) reported a one-pot transamidation of cinnamamide

• cinnamamides 13, 77, 99, and 371 in good yields via the active palladium–hydride species 372 (Scheme 81A) [137]. The Z-to-E-selectivity could be effectively tuned by changing the solvent and temperature from CH3CN to DMF and rt to 80 °C, respectively. Similarly, Wang and co-workers (2023) employed Pd to

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• dissolved or suspended in water, and the resulting mixture transferred to an autoclave and treated at a temperature ranging 140–200 °C; the treatment yields CDs with an amorphous structure. The synthetic procedure, as well as the structural and morphological characteristics of these materials, have been

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• problems in the future and prepare organic radicals for the challenges in emerging quantum technological applications. Review Triarylmethyl monoradicals The importance of symmetry in triarylmethyl radicals Gomberg’s radical is unstable at room temperature and dimerizes quickly to a closed-shell molecule

• mixture of right- and left-handed propellers can be resolved by chiral high pressure liquid chromatography (HPLC) into the P- and M-enantiomers, respectively [40][41]. However, due to the low racemization barrier of only about 22 kcal mol−1, the enantiomers racemize within minutes at room temperature. TTM

• )methyl (TTBrM) radical exhibits λem = 593 nm and ϕ of 0.8% (in dichloromethane-solution, at room temperature) [50][51]. Functionalization of TTM in the para-position has also been achieved with a pseudo-halide, namely a nitrile group. While the absorption and emission spectra are slightly

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• ester 29 gave pyrrolo-β-carboline 30 in excellent yield (Scheme 7). Our attempts for the selective saturation of the pyrrole ring of 30 by catalytic reduction were unsuccessful. When the hydrogenation was carried out under mild conditions (ambient temperature, 15 bar H2) in the presence of PtO2.H2O

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• equivalent of commercial iodomesitylene diacetate (CAS [33035-41-5]) and 1 equivalent of MsOH (Table 1, entry 4). Here, it was necessary to maintain a temperature of 0 °C, as vigorous bubbling and rapid decomposition occurred when the reaction was initiated at room temperature. In all cases (Table 1), only a

• delivering product (Table 2, entries 1 and 3–5). With our standard conditions of stirring substrate with 1.5 equivalents of PhI(OH)(OTs) in CH2Cl2 at room temperature, the yield of product markedly suffered with N-isopropoxy carbamate substrate 3 (Table 2, entry 2). Here, we hypothesize that the increased

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• , with values of 16%, 14%, and 14%, respectively. The lowest values were obtained for molecules 5a and 5b (7% and 6%, each). Remarkably, compound 5e demonstrated minimal luminescence in nearly all solvents at room temperature. This behavior has been previously reported and is believed to be due to strong

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• 10 was unequivocally determined through X-ray crystallographic analysis (ORTEP drawing, Scheme 4). Further optimization by elevating the reaction temperature did not noticeably alter the ratio of 32 and 33 (Table 1, entries 8 and 9). Moreover, attempts to apply interrupted Nazarov cyclization with

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• , when performed at room temperature, proceeded with lower efficiency compared to the reaction at 70 °C, leaving some of the starting 1H-pyrazole-3-carbaldehyde (14a) unreacted. Propargylamide 15a was selected as a model substrate to optimize the reaction conditions for the intramolecular

• temperature to 90 °C and the catalyst loading to 10 mol % enabled full conversion of 15a and improved the yield of product 16a (Table 1, entries 2 and 3). The use of other silver salts including AgBF4, Ag(NTf)2 and AgNO3 did not lead to improved results, with Ag(NTf)2 being particularly ineffective (Table 1

• temperature. cConducted on a 2.0 mmol scale. dConducted on a 1.5 mmol scale. Scope of the silver(I) triflate-catalyzed synthesis of pyrazolo[1,5-a][1,4]diazepines. Conditions: Unless otherwise specified, the reactions were run on 0.2 mmol scale using 20 mol % of AgOTf in dioxane (1 mL). The reactions were

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• literatures focusing on key regulatory factors for product divergent formation, in which controlling chemical selectivity primarily relies on ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates. To gain a deeper understanding of the mechanisms underlying

• review systematically examines, how these multidimensional control elements (including ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates) synergize to achieve predictable product diversification. In addition, mechanistic insights are discussed

• (cod)Cl]2 and the Carreira chiral phosphoramidite ligand (S)-L10, along with the addition of 3,5-dichlorobenzoic acid as an additive in MeOH at room temperature, the reaction proceeded smoothly for 10 hours to yield the aminated product 51. Interestingly, when the reaction was quenched after 6 minutes

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• product in 70% yield with 83:17 dr by decreasing the reaction temperature to 50 °C (Table 2, entry 4). Under the same optimal conditions, compound 8 could be transformed into cyclopropane 17 in 61% yield with 81:19 dr (Table 2, entry 5). It is important to note that (2,2-dichlorovinyl)cyclopropanes

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• (acac)2) and chitosan-supported on CuSO4 (CS@CuSO4) were explored, and the results showed that CS@CuI was the most effective catalyst (Table 1, entries 7−11, 65−89% yields). To further enhance the reaction yield, the reaction temperature was increased to 90 °C, and the target product 3a was obtained in