Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• starting diazoketone 1a–i and l, while under the conditions used it was not possible to achieve complete conversion of diazoketones 1j,k and the yield of compounds 5n,o was 18 and 23%, respectively. The first step of the reaction fails with aliphatic aldehyde (propanal) and the weakly electrophilic N

• -methylpyrrole-2-carbaldehyde and 4-hydroxybenzaldehyde, likely due to a shift in equilibrium toward the starting compounds. The reaction with strongly electrophilic, acceptor-substituted aromatic aldehydes, 4-nitro-, 4-cyanobenzaldehydes, and pyridine-4-carbaldehyde, is accompanied by complete resinification of

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• facial selectivity during electrophilic trapping. These findings expand the synthetic utility of α-boryl lithium intermediates and provide insight into the origins of their diastereoselectivity. Keywords: α-boryl lithium; diastereoselectivity; (iodomethyl)cyclopropylboronic esters; ring-opening

• diverse catalytic and stereoselective transformations [28][29][30][31][32][33]. In this context, we have recently demonstrated that a broad range of arylated (iodomethyl)cyclopropylboronic ester 2 [34] undergo ring-opening reactions, followed by electrophilic trapping of the resulting α-boryl carbanion

• regioselectivity. The use of various electrophiles enabled the synthesis of acyclic boronic esters featuring vicinal tri- and tetrasubstituted stereocenters. Cyclopropylmethyl iodide starting materials. Synthesis and reactivity of α-boryl lithium species. Diastereodivergent electrophilic trapping of α-boryl

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• proteins, including somatostatin, immunoglobulins (across all isotypes and subclasses), insulin and interleukin-10 naturally contain disulfide bridges. These can be selectively reduced to yield two nucleophilic thiols for reaction with bis-electrophilic reagents to rebridge the cysteines, while introducing

• for enzyme modification [46]. This concept evolved into activity-based protein profiling (ABPP), pioneered by the Cravatt group, where peptides or small molecules bearing electrophilic groups covalently react with active-site residues, enabling phenotype-driven functional profiling in a complex

• substrate profiling. Affinity-guided labelling. a) Reagents and catalysts appended to the binder include electrophilic motifs 14–17 as well as b) benzophenone 18, c) rhodium complexes 19, d) 4-dimethylaminopyridine 20 (DMAP), and e) pyridinium aldoxime 21 (PyOx). Chemical sequence to convert subtilisin

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• H–H bond cleavage had been reported earlier by Rocchigiani et al. for the highly electrophilic ether adduct [(C^N–CH)Au(C6F5)OEt2]+ which shows “frustrated Lewis pair” (FLP)-like reactivity (Scheme 7) [32]. The electrophilic character of CO ligated to gold explains why gold is more active than

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• approaches [2][3][4][5]. In this context, comprehensive medicinal chemistry studies consistently highlight the prominence of isatin-derived frameworks among bioactive and anticancer agents [6]. The remarkable reactivity of the isatin scaffold arises from its dual functionality, combining an electrophilic C-3

• complexity and, in some cases, unexpected reaction outcomes. In reactions involving amino acids or diamines, the coexistence of multiple nucleophilic and electrophilic sites can give rise to competing pathways and polycyclic architectures. A well-documented example is the condensation of isatin (1) with ʟ

• and 24 may coexist in equilibrium. The diimine 24 could also be in equilibrium with its tautomeric form 27. If the enol present in 27 attacks intramolecularly the other imine, it would produce a non-stabilised imine 28, which would be electrophilic and hence susceptible to reduction either by the

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• . Specifically, solvation by aprotic DMF having a high dipole moment promotes the formation of the [Na+–diazafluorenyl−] ion pair, whose anion displays insufficient nucleophilicity for interaction with weakly electrophilic aldehydes (e.g., benzaldehyde and 4-methoxybenzaldehyde). On the other hand, tert-butanol

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• experimental and computational study of the diastereoselectivity of cyclic sulfone synthesis by reaction of Rongalite with doubly electrophilic dienones is presented. Computational methods, including density functional theory, conformational search methods, and internal reaction coordinate methods, have been

• (indicated). There is nothing to suggest from the calculations that an inherent reactivity problem prevents the initial addition of Rongalite to the enone, especially given that the singly electrophilic 2,6-dimethylbenzalacetone is known to participate in reactions with conjugate nucleophiles [25]. It is

• donors [47] or, given the high solubility of Rongalite in water, phase-transfer catalysis [48]. Our earlier results indicate that tolerance of steric effects is greater in reactions with doubly electrophilic substrates that render the second conjugate addition intramolecular, justifying our choice of

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• from imino esters, catalyzed by chiral Cu(I,II) and Ag(I) complexes, are widely used. Reactions using α-amino acids proceed, in most cases, without the use of catalysts, with high yields and high stereoselectivity. Electrophilic alkenes of various structures, (hetero)aromatic olefins and benzofulvenes

• compounds were reviewed. Rare methods for preparing azomethine ylides using pyridylimines and α-silylimine were described. Electrophilic alkenes, styrene derivatives, and new, previously undescribed unsaturated substrates were frequently used as dipolarophiles. The contribution of our research group to the

• iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• that CF3· behaves as an electrophilic radical [31][32], it was expected to react preferentially with electron-rich substrates compared to electron-neutral or electron-deficient ones. To probe this trend, trifluoromethylation was examined with substrates bearing donor substituents (methoxyarenes) and

• CF3 radical, is an endothermic process. The subsequent attack of the electrophilic CF3 radical on the benzene ring, accompanied by its oxidation, proceeds through exothermic steps. The proton transfer to the solvent constitutes the most favorable step, resulting in an overall free energy change (ΔG

• that the addition of the electrophilic CF3 radical to the aromatic ring may differ in energetic profile between the two substrates (Scheme 5). However, DFT calculations showed that the thermodynamic parameters for both processes are comparable, indicating that other elementary steps may be responsible

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• . These properties encompass the site of metabolism [25][27], the strengths of hydrogen bond donors and acceptors [28][29][30], the regioselectivity of electrophilic aromatic substitution reactions [10], C–H pKa values [3], and electro- and nucleophilicity [31]. Building on the methodology from Finkelmann

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