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

• ], antioxidant [34], cytotoxic [35], and antiproliferative [36]. The structures of these compounds allow the synthesis of a large collection of bioactive molecules due to their nucleophilic and electrophilic properties [37]. One of the forms of modifications is at the methylene group, particularly in the 5

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

• Studer et al., which belongs to the class of aryl and heteroaryl electrophilic substitutions and is a highly versatile synthetic transformation in traditional organic chemistry. A highly regioselective dual catalytic approach for the novel acylation of electron-rich benzo-fused arenes or heterocycles 15

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• -3-yl lithium derivative, followed by electrophilic trapping of the thiolate and base-induced cyclization to afford the 3-hydroxy-TT [25]. Route II is represented by the single example of a one-pot reaction of 2-methylquinoline and 3-bromothiophene-2-carbaldehyde in the presence of elemental S and

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

• and functional materials (Scheme 1a) [62][63][64][65][66]. Traditional electrophilic aromatic substitution methods for the nitration of carbazole typically result in a mixture of 1-nitro-, 2-nitro-, and 3-nitro-substituted isomers (Scheme 1b) [67]. Therefore, developing a method for the regioselective

• ). Plausible catalytic cycle. (a) Representative examples of bioactive nitrocarbazoles. (b) Traditional electrophilic aromatic substitution approach for the nitration of carbazole. (c) Present work: palladium-catalyzed directed C1-selective nitration reaction. Effect of directing groups on the nitration of the

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

• donor; haloacetimidates; haloacetonitrile; two-chamber reactor; Introduction Trifluoroacetonitrile is an electrophilic reagent that has seen a variety of uses, mostly for incorporating trifluoromethyl groups into organic compounds [1]. As an example it has been successfully utilized for the synthesis

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

• efficiently constructed by catalytic asymmetric hydroselenation, catalytic asymmetric allyl substitution, catalytic asymmetric electrophilic selenylation/cyclization, etc. The research content of this part has already been covered by relevant reviews [15][16][17], so it is not within the scope of discussion

• and Outlook Overall, organic chemists have increasingly focused on the catalytic asymmetric synthesis of selenium-containing atropisomers, and significant progress has been made in recent years. Nevertheless, several limitations and challenges remain. For example, catalytic asymmetric electrophilic

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

• to explore additional protecting groups for the hydroxy functionality. Furthermore, given that alkylidene carbenes are electron-deficient and highly electrophilic, electron-rich C–H bonds are more prone to undergo C–H insertion [48]. Following this analysis, commencing from 20, after reduction, the

• developed an approach to assemble the bicyclic skeleton of vibralactone (6) utilizing an intramolecular alkylidene carbene C–H insertion as key step. The insights gained from this study illustrate how diverse reactivity patterns and electrophilic characteristics of alkylidene carbenes influence ring closure

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

• , ketone reduction, hydroquinone oxidation, and alcohol oxidation – led to the labile ketone 118. Completion of preussomerin EG3 (99) from 118 relied on a simple sequence including a formal intramolecular 1,6-addition, followed by simultaneous methanol trapping of the resulting electrophilic quinone

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

• -surfaces and which are activated for electrophilic aromatic substitution reactions. For the synthesis of W1, we initially prepared tetramethoxybiphenyl 1 (Scheme 1) according to the literature procedure involving the Suzuki coupling between 3,4-dimethoxybromobenzene and 3,4-dimethoxyphenylboronic acid [44

• discern the effect of smaller aromatic sidewalls. The synthesis of acyclic CB[n]-type receptors follows a building block approach involving the reaction of a glycoluril bis(cyclic) ether with an activated aromatic wall by a double electrophilic aromatic substitution process [30]. Scheme 2 shows the

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

• been reported in a 12-step procedure starting with glucose in an overall yield of 2% [24]. Enol esters [25], enolates [26], enamines [27][28], and silyl enol ethers [29], some of which can be derived from LGO, have been used in electrophilic fluorination and trifluoromethylation strategies. It was

• monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can

• electrophilic fluorine in the best case gave 15% conversion for NFSI and less than 8% isolated yield of 7c for SF. The major product in these reactions was 5, due to a β-elimination of the amine. In comparison, the reaction of 15 with NBS afforded 7b in an unoptimized yield of 48% after hydrolysis, which

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

• , a relatively electrophilic radical could readily add to a nearby electron-rich olefin, and the resulting nucleophilic radical could add to an electron-poor olefin (e.g., substituted with a cyano group). In one example, polyene 15 underwent cyclization to afford hexacyclic product 17 with 93% ee in a

• reported intramolecular Giese-type radical cyclization reactions involving unstabilized alkyl radicals generated from alkyl iodides (Scheme 8) [34]. The generation of unstabilized, nucleophilic alkyl radicals from alkyl iodides was more challenging than the generation of more electrophilic alkyl radicals

• enantioselective transformations of electrophilic radicals, alternative H-atom sources, and additional modes of catalysis (including hydrogen-bonding catalysis) would be valuable. Additionally, the development of more efficient methods, using lower catalyst loadings, remains an important goal for ongoing research

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

• biomass shows how renewable carbon sources can replace non-renewable chemicals in important industrial processes [18][19][20]. Many, if not most, biobased platform molecules contain carbonyl groups. Carbonyl compounds have unique electrophilic and nucleophilic reactivity which make them central players in

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• electrophilic reagents. This site offers a strategic handle for introducing diverse substituents to modulate the compound's properties. Although the indolo[1,2-c]quinazolin-6(5H)-one scaffold offers considerable potential for structural diversification, current literature describes only the arylation at

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• sufficiently electrophilic carbonyl carbon atom with the elimination of triphenylphosphine oxide via the aza-Wittig reaction. It should be noted that the best method for the isolation of quinoxalinones 9 was column chromatography using an elution gradient of hexane/ethyl acetate 3:1 to hexane/ethyl acetate 1:2

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

• synthetic potential of iodane-mediated carbofunctionalization under copper catalysis. Keywords: arylation reactions; copper-catalysis; iodanes; propargylsilanes; 1,2-silyl shift; Introduction Highly electrophilic hypervalent iodine(III) reagents are considered as arene electrophilic synthons, making them

• alkynes undergo 1,2-carbofunctionalization, where the highly electrophilic Ar–M species adds to the alkyne, generating a vinyl cation intermediate [7], which typically reacts with an internal nucleophile to form five- [8][9] or six-membered rings [7][9][10] (Scheme 1A). Thus far the internal nucleophilic

• ) salt reacts with the diaryl-λ3-iodane (ArMesIY) to generate the strongly electrophilic arylcopper(III) species. The latter activates the propargylic system to induce the 1,2-silyl shift, producing the allylic cation intermediate Int-4, which is stabilized by the β-silicon effect. A following attack of

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• intermediate A (Figure 1a), in which the formerly electrophilic carbonyl carbon reacts as a nucleophilic center. In this way, the traditional reactivity profile of the carbonyl group is transiently inverted, and unconventional product classes are generated. Alternatively, addition/elimination of the NHC to a

• suitably electrophilic substrate at the carboxylic acid oxidation level provides an acylazolium species B, which typically reacts directly with nucleophiles or may first be transformed into the corresponding enolate derivative. Regardless of the individual pathway, NHC-catalyzed reactions of this type

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -deficient [28], thereby lowering the energy barrier for electrophilic radical addition. Increasing the reaction temperature to 70 °C proved detrimental, yielding only trace amounts of product 14 (Table 1, entry 5). Finally, replacing Mn(OAc)3·2H2O/Cu(OAc)2·H2O with other oxidants, such as ceric ammonium

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

• , wherein one hydroxy group underwent nucleophilic attack on the C2 electrophilic center while the other remained unreacted, giving furoindoline 284 in 45% yield. A final two-step transformation completed the synthesis of (−)-ψ-akuammigine (285). In 2021, the Ding group reported the total synthesis of two

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• ][3]. Established sets of reactive probes are typically armed with electrophilic warheads that have the potential to target nucleophilic amino acid side chains. Most reactive probe sets bear cysteine-directed warheads [3][4][5][6][7], although sets have also been designed to target a wider range of

• that all of these active compounds are 4-phenylpiperidinyl amides derived from the same α-diazoamide 2, suggesting that this feature is important for activity. Conclusion We have developed a connective synthesis of reactive probes bearing S(VI) electrophilic warheads. Each probe was prepared by rhodium

• ) electrophilic warheads (WH). Diverse probes 3 might be accessible by functionalising α-diazoamide substrates 2 via alternative reaction modes. Structures and reactions of co-substrates. Panel A: structures of the 16 selected co-substrates C1–16, together with two additional co-substrates C17 and C18 that were

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• through a [3 + 3]-cycloaddition reaction. By employing the CPA-catalyzed asymmetric electrophilic amination reaction with azodicarboxylate on the phenol moiety, efficient kinetic resolution of 25 proceeded to yield both the amination products 26 and the recovered starting material with high

• electrophilic amination reaction of the aniline moiety with azodicarboxylates [37][38], the introduction of a bulky hydrazine group restricted the free flipping of the benzene ring, leading to the formation of planar chiral macrocycle 33 with high enantioselectivity (Scheme 9). Substrate scope studies

• directly used as a planarly chiral primary amine catalyst in the asymmetric electrophilic amination reaction of aldehyde 34, which yielded the α-amination product 35 with high enantioselectivity. In 2022, our group disclosed an enantioselective macrocyclization protocol for the asymmetric synthesis of

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• corresponding imines I and I′, as supported by the detection of imine I during GC–MS analysis. Both imines coordinate with the Lewis acid FeIII forming intermediates II and II′ with enhanced electrophilicity, respectively. Another equivalent of styrene (2a) attacks the electrophilic carbon, leading to the

• formation of intermediates III and III′. Subsequent electrophilic cyclization/C–H annulation of the aromatic amine, followed by aromatization, afford intermediates V and V′. The oxidative dehydrogenation of intermediates V and V′ then results in the formation of products 3a and 3a′ and the regeneration of

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• classified into two major types: (1) σ-type halogen bonding, where the electrophilic region (σ-hole) of a halogen atom interacts with a lone pair on an electron-rich atom (e.g., C–X···Y), and (2) π-type halogen bonding (or halogen–π interaction), where the σ-hole interacts with an electron-rich π-system (e.g

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• aliphatic counterparts) due to their predictable electrophilic substitution mechanisms and relatively mild reaction conditions, which enable superior controllability and regioselectivity. Unlike aromatic nitrations that predominantly follow ionic mechanisms, aliphatic systems governed by free radical

• suppressing byproduct formation from over-sulfonation and minimizing environmental burdens through reduced waste acid discharge. Water content governs the formation equilibrium of nitronium ions (NO2+), the electrophilic nitrating species, thereby dictating the overall reaction rates. In nitration processes

• dehydration. This electrophilic species subsequently engages in an aromatic electrophilic substitution, with reaction kinetics heavily influenced by the electronic nature of substituents and acid strength. Table 2 analyzes studies in the literature that utilize the flow-chemistry technology to investigate the

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• of the resulting products in developing chiral organocatalysts was investigated as well. For instance, 28a was converted to a thiourea-tertiary amine 29 through a four-step procedure in an overall 36% yield. This compound was then utilized as the catalyst in the electrophilic amination reaction

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• -containing compounds [1][2][3]. Such reactions can be initiated by electrophilic, nucleophilic or radical reagents, photoirradiation or proceed under acid-, metal-, or photocatalytic conditions. This strategy of azirine ring expansion is applicable to the synthesis of a variety of 4‒9-membered N-heterocycles