Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• (I). Indeed, the Friedel–Crafts acetylation of cymantrene, a typical electrophilic aromatic substitution reaction, is much slower than that of ferrocene. Consequently, vinylcymantrenes are electron-deficient olefins and less reactive in olefin metathesis. For this reason, the present AMD/KR reactions

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• )/Cr(II)-mediated coupling of 1-bromo-2-trimethylsilylethene, acidic cleavage of the remaining cyclohexylidene ring, TBDMS-protection of the three alcohol units and electrophilic substitution of the silyl moiety to afford vinyl iodide 103 was applied. Eventually, ester 103 was reduced to target

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• demands of the proliferative state creates an opportunity to selectively target cancer cells [1][7]. Chemical inhibition of GLS has emerged as an attractive anticancer strategy, and several classes of GLS inhibitors have been discovered [1][2]. DON is a diazo-containing electrophilic glutamine analog that

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• products were detected under the optimized conditions (Scheme 2). Based on our previous reports [48][56], DFT calculations, and cyclic voltammetry (CV) analyses (Figure 1), anodic single-electron transfer (SET) is expected to occur first from 3, generating the electrophilic radical cation [3]·+ as 3 (Eox

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• catalysis, electrophilic activation, strong base-counter-cation systems, and N-based activating groups that enable chemoselective bond cleavage. Together, these developments provide powerful tools for amide functionalization and offer new opportunities for efficient, practical, and selective syntheses

• , such methods often exhibit limited substrate scope, generally restricted to amides with low steric hindrance, such as DMF or DMAC. In recent years, several new strategies have emerged to overcome these limitations: (i) transition-metal-free activation using electrophilic reagents, (ii) strong-base

• generates a reactive intermediate I. Subsequent exchange of L1 with benzylamine enables intramolecular nucleophilic attack, leading to transamidation. Transition-metal-free electrophilic activation Since the keteniminium ion, which can be readily generated by electrophilic activation of enolizable tertiary

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• addition towards the highly electrophilic α-diketone moiety. With this, the bicyclic lathyrane skeleton of jolkinol C (45) is assembled selectively from casbene. The large family of indole meroterpenoids [94][95][96][97][98] also contains an interesting, enzyme-mediated ring-expansion reaction. According

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• disrupting the aromatic core, such as electrophilic and nucleophilic aromatic substitutions, transition metal-catalyzed cross-couplings [11], and C–H functionalizations [12]. Taken together with their natural abundance, these transformations have established arenes and heteroarenes as versatile synthetic

• of π-bond localization in arenes and its influence on reactivity can be traced back to the early 1930s, when Mills and Nixon investigated how the annelation of small rings to aromatic systems influences the regioselectivity of electrophilic substitutions in tetralin vs indane (Figure 3A) [16

• ; Figure 4B) [44][45][46]. Collectively, these changes alter the innate reactivity of the arene, steering η2-coordinated systems toward electrophilic addition, cycloaddition, and hydrogenation processes. While many transition metals can engage aromatic rings through η2-coordination, only a handful have

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• renders the pyranoquinoline carbonyl more electrophilic than that of the acyclic ester, facilitating its alcoholysis at elevated temperature and extended reaction times. Consequently, pyranoquinolines may be regarded as kinetic products, formed rapidly under mild conditions, whereas the open-chain esters

• represent thermodynamically favored, more stable products formed upon prolonged heating. To support the hypothesis that the carbonyl carbon atom in pyranoquinoline exhibits higher electrophilicity than in the open-chain ester, quantum chemical calculations were performed to evaluate their electrophilic

• quantification was performed using a set of quantum chemical descriptors that describe electrophilic properties of an atom: Fukui atomic index, f+ [46], condensed local electrophilicity index, ω, condensed local softness, s+, and relative electrophilicity index, s+/s− [47] (Table 1). These quantities

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• [11][12][13][14]. The highly polarized S–O bond imparts distinctive reactivity, making them promising modular electrophilic intermediates for the construction of complex and functionally rich sulfur–nitrogen architectures [14]. Despite their synthetic potential, general and efficient methods for the

• sulfenamide precursors [35]. These studies collectively underscore the synthetic potential of sulfenamides as central electrophilic platforms [36] and the advances regarding the synthesis and reactivity have been comprehensively reviewed very recently [37]. Nevertheless, existing protocols, including our own

• limitations, we envisioned that highly electrophilic sulfilimidoyl intermediates – generated in situ via N-halosuccinimide-mediated oxidative activation of sulfenamides – could be directly intercepted by alcohols under basic conditions to furnish structurally diverse sulfinimidate esters [32]. In particular

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• -Petersburg 199034, Russia 10.3762/bjoc.22.5 Abstract New highly electrophilic gem- and spiro-activated trichloromethylnitrocyclopropanes were obtained by the Michael-initiated ring closure (MIRC) reaction of 1-bromo-1-nitro-3,3,3-trichloropropene with linear and cyclic CH-acids catalyzed by bases

• of ring opening or expanding [11][12][13]. Thus, known trichloromethyl-containing cyclopropanes can serve as precursors for hard-to-access halogenated β,γ- and γ,δ-unsaturated esters [14][15]. Nitrocyclopropanes are known as highly electrophilic substrates and can form a carbanion stabilized by the

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• reactions mainly involve the initial electrophilic attack onto the α-position relative to the hydrogen atom. The selectivity is either due to the high stability of the α-nucleophilic conformer or due to the promotion by the adjacent ester group. Cascade reactions upon the target connection, if installed

• potassium 1 (Figure 2) undergoes reactions with various electrophilic reagents which presented the first examples of unexpected pathways for the derivatization of cycloheptatrienes [17][18][19]. However, the anion is highly symmetric and does not challenge regioselectivity. Therefore, besides the

• isomer of anion 2 we analyzed the structure of its highest occupied molecular orbital (HOMO) and the distribution of the electrophilic Fukui function (f–) [28] – the difference in electron density between the anion and the derived radical by abstraction of one electron (Figure 2). Both approaches

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• oxidation of HCl with oxone (potassium peroxymonosulfate) to generate molecular chlorine (Scheme 35A) [135]. Electrophilic addition of chlorine across the enone double bond, followed by triethylamine-induced elimination, furnished the corresponding alkenyl chlorides (e.g., compound 193) in good yields. A

• –chlorine exchange reagent and as a base. Similar exchange reactions with AlCl3 and 1,1,1-trifluoroalkanones were recently reported by McLeod and co-workers (not shown) [141]. 1.6 Electrophilic additions to alkynes Melloni was the first to report the addition of alkynes to in situ-generated tertiary

• , potentially forming a transient chloronium ion (CH2Cl+). Reaction of this electrophilic intermediate with the BF4− counterion would be expected to yield CH2FCl and BF3; however, the authors did not investigate or confirm the formation of these by-products. In 2006, Cook reported a related cyclization

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• -ditosyloxy ketones. It is found that the mechanism for the formation of α,β-ditosyloxy ketone involves only electrophilic addition of HTIB, and the mechanism is the same for all studied chalcones, irrespective of whether an electron-donating or electron-withdrawing substituent is present on the aryl ring

• . However, the detailed mechanism for the formation of β,β-ditosyloxy ketones is different and depends on the nature of the substituent. Broadly, the formation of β,β-ditosyloxy ketones involves electrophilic addition followed by 1,2-aryl migration. Our study shows that the presence of an electron-donating

• differences as given in parenthesis for all studied substituents including -OCH3. Overall both in Scheme 2 and Scheme 3, the reaction between chalcone and HTIB proceeds through electrophilic addition of [PhIOH]+ followed by nucleophilic addition of −OTs. In the beginning electrophilic addition occurs on the

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• , thioethers, disulfides, phosphonothioates, and trifluoromethyl sulfides. Additionally, due to the presence of two electrophilic sites (the sulfur atom and the carbon of the nitrile function), thiocyanates can readily undergo domino-type intramolecular cyclization reactions to form heterocycles. So, if a

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• reaction of compound 15, regioisomer 8 was also isolated in 2% yield, which represents a new ring system, too. It is interesting to mention that the formation of a similar isomer was not observed in the cyclization reaction of compound 14. The same disparity was observed in the studies of electrophilic

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