Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• in this system was confined to electrophile activation, with the C–N bond formation proceeding via a classical Lewis acid-mediated aza-Michael pathway. Yamazaki et al. reported that the conjugate addition of aromatic amines to highly activated ethenetricarboxylates 16 can be promoted by copper

• catalyst plays multiple roles, including the generation of Michael acceptor, activation of the electrophile, and facilitation of the annulation step, enabling the efficient construction of N-alkyl 2-arylindoles. Heterogeneous processes: copper nanomaterials Scheme 11 summarizes the representative examples

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

• revealed that the electrophile preferentially approaches from the face opposite the coordinating lithium cation, with the lowest-energy transition state stabilized by a lithium cation–vinyl interaction (see A in Scheme 1) [34]. Results and Discussion The intricate interplay of the coordination and steric

• electrophile PhMe2SiCl did not alter the selectivity of the transformation, yielding 6b as a single diastereomer (Scheme 3). The relative configuration of 6b was determined by X-ray analysis of the osmate ester 7b, derived from osmium-catalyzed dihydroxylation (Scheme 3) [38], and the other products were

• confirmed due to the inability to obtain suitable crystals for X-ray analysis. In addition to the nucleophilic substitution of the boryl lithium species with R3SiCl, a small range of alternative electrophiles was examined (Scheme 3). Incorporation of a tin-based electrophile furnished stannane 6i in

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

• composed of (1) an affinity ligand that binds to a localised region of a target protein, and (2) a reactive moiety, either a pre-installed electrophile or a catalytic unit that generates one. Once bound, the reactive group is transferred to the target protein, enabling covalent modification. This concept

• strategies broadly classified into non-catalytic and catalytic approaches. Non-catalytic approaches often involve tethering a reactive electrophile to a protein-binding ligand, thereby positioning the electrophile near a neighbouring nucleophilic residue. Example electrophiles include 4

• nearby target residue such as histidine (Scheme 11a) [105], aspartate (Scheme 11b) [106] and lysine (Scheme 11c) [107]. For example, reagents containing o-hydroxybenzaldehyde (31, 32) and β-nitroalkene (33) can reversibly engage lysine and cysteine residues, respectively, while a proximal electrophile

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

• . In 2021, the Evano group developed a double electrophilic activation strategy for tertiary amides using trifluoroacetic anhydride (Tf2O) and N-fluorobenzenesulfonimide (NFSI), enabling α-fluorinative C–N bond cleavage (Scheme 9) [57]. In the presence of 1.5 equivalents of Tf2O as an electrophile and

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

• with the formation of 4a,b, as well as the formation of hydrazone product 10k exclusively in the case of the most sterically hindered diazonium electrophile leads to the conclusion that the direct electrophilic attack onto the i-position could take place in all these cases. To clarify this, we analyzed

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

• demonstrated that halogenation reactions with 15 were viable, but dependent on the characteristics of the electrophile. To avoid the elimination of the amine, β-methyl ether 16 was prepared. The reaction of ketone 16 with Selectfluor promoted by ʟ-proline in MeOH/MeCN, which ensured that the equilibrium

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

• cross-electrophile coupling of alkyl halides and nitroalkanes [76]. Yang and co-workers reported photoenzymatic asymmetric C(sp3)–C(sp3) oxidative cross-couplings between organoboron reagents and amino acids (Scheme 9) [37]. The authors used a synergistic system consisting of an engineered threonine

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

• oxygen in alcoholic medium has also been reported (Scheme 37) [121][122]. Riguet synthesized γ-lactams through a Ugi 4-center 3-component reaction (U-4C-3CR) protocol. HFO was used as the electrophile in the Friedel–Crafts (FC) alkylation reactions of indole catalyzed by diphenylprolinol silyl ether. The

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

• using the symmetrical dithiophen-2-yliodonium p-tosylate (I-7). It should be noted that all products 8 were obtained with exclusive (E)-selectivity. Tetrahydrofuran 8a and some analogous compounds could be synthesized previously from alcohol 7d, but in two steps, employing a halogen electrophile-induced

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

• provide an electrophile capable of trapping the putative alkoxide zwitterionic intermediate E, outcompeting O-benzoylation by a second molecule of 1. Pleasingly, conducting the standard photocatalyst-free reduction of 1 with 1 equivalent of DIPEA under UV-A light irradiation (λmax = 370 nm) in the

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

• the reactive probes would be prepared by dirhodium-catalysed reactions between pairs of building blocks: an α-diazoamide 2 bearing a S(VI) electrophile and a suitable co-substrate (→ 3) (Figure 1). Here, metal-catalysed carbenoid chemistry was chosen because of the wide range of potentially reactive

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

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

• ][59][60]. This scheme also enables control of the number of formyl groups by starting materials and reagents. Brominated [4.3.3]propellane was reacted with n-BuLi or iPrMgCl·LiCl to generate an organometal species, which was quenched with N,N-dimethylformamide (DMF) as an electrophile (Table S201 in

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

• in their laboratory. The strategy primarily involved the reaction of a chiral organometallic reagent 115 with a chiral allyl electrophile 114, as depicted in Scheme 18. The resulting deoxypropionate 113 was obtained with the newly formed stereocenter controlled by the reagent directing group (RDG

• 124 was obtained by reaction with magnesium in anhydrous diethyl ether. Herber and Breit emphasized that activating the magnesium using a dry stirring method was crucial for smooth magnesiation. The freshly prepared Grignard reagent 124 was added to the allyl electrophile (R)-120 in the presence of

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• internal rotation in 11 via TS8 and reaction with TMSCN to give adduct 13 (see Figure 3). Distances and bond lengths are given in pm. Catalyst 7 is replaced in TS 11-12 by concerted electrophilic intramolecular substitution with formal trimethylsilyl cation as electrophile. Please note the surprisingly

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

• to avoid precipitation of the compounds 7, 8, 9, and 11 during long (>12 h) incubation times). In view of these results, we further focused on HBC derivatives with the high-yielding C3 handle and sought a variation of the electrophile. Thus, adapted Appel reaction conditions using N-chlorosuccinimide

• RNA. Key is the functionalization of the original N-(2-hydroxyethyl) moiety into a reactive handle providing a mild electrophile (LG), such as, e.g., N-(3-bromopropyl) or N-(3-mesyloxypropyl) [11]. Pepper aptamer reacts with different HBC derivatives. Chemical structures of the HBC derivatives used

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

• dependent on both the leaving group of the allylic electrophile and the choice of the supporting ligand. When (+)-1,2-bis{(2S,5S)-2,5-diphenylphospholano}ethane {(S,S)-Ph-BPE} (L1) was employed as the supporting chiral ligand, initially allylic chloride was found to provide the desired product 32 with

• the competing transition states showed that the chiral α-borylalkylcopper species 37 could approach the olefinic moiety of allylic electrophile 35 from either the re- or si-face. The re-face approach is energetically favored, minimizing steric interactions between the bulky aryl substituent of NHC

• ligand L3 and the allylic electrophile 35. In contrast, a si-face attack leads to a higher-energy transition state due to significant steric repulsion. Enantioselective hydroallylation of vinyltrifluoromethyl compounds The direct functionalization of 1-trifluoromethylalkenes 38 through copper catalysis

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

• transformations is a strong electrophile that can react with Tyr, for instance, if such an amino acid is located near the reactive site. In addition, command of the DAR might have some limits, as the distance between the catalyst and the mAbs is not well defined, meaning that the photoredox reaction might not

• method allows the same photocatalyst and electrophile to be involved in two different but selective bioconjugations of mAbs. It remains limited to reactions involving oxidative mechanistic pathways with 1O2. Cys In 2016, Bräse et al. developed a photomediated disulfide rebridging method, exploiting the

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

• products (products 2 to 5, Scheme 4). In other cases, under acidic and thermal conditions, DMSO can undergo a Pummerer-type process in which, upon activation of the sulfoxide oxygen, a reactive methyl(methylene)sulfonium ion (MMS) is formed (Scheme 5) that acts as an active electrophile. Depending on the

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

• ] as electrophiles. It is noteworthy that the development of such vinylogous functionalizations of this nitrogen heterocycle with a fluorine-containing electrophile may be of interest to pharmaceutical and medicinal chemists. Results and Discussion 4-(Alkenyl)-5-aminopyrazoles 3 were selected as

• electrophile activation. In certain reactions, we isolated compound A, the hydrate of methyl trifluoropyruvate. We hypothesized that preventing the formation of this byproduct could improve the reaction yield by using molecular sieves (entries 17 and 18, Table 1). However, when molecular sieves were added, the

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

• vitro and in living cells using rationally designed electrophile-tethered derivatives of preQ1 (1) and its Watson–Crick diamino-faced counterpart DPQ1 (2, Scheme 1A). These ligands (compound classes 3 and 4, Scheme 1A) were tailored to target a conserved guanine nucleobase within a natural preQ1-binding

• of the electrophile. We thus identified aldehydes 9 and 10 as suitable branching points, which were easily derivatized to their aminomethyl-modified preQ1 analogs by reductive amination (Scheme 3). Their syntheses by Raney-Ni reduction of nitriles 7 and 8, previously described by Gangjee and co

• . First, the alkyl handles bearing a primary hydroxy group were introduced and then converted into the electrophile of choice. More specifically, to furnish compounds 4b–d, precursor 9 was treated with the corresponding amino alcohols in the presence of a desiccant. The imines formed were subjected to

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

• nucleophile and electrophile) [5][6][7][8][9][10][11][12]. Crucially, enzymes organize their polarization – they achieve both components in tandem. Supramolecular chemists have made significant advances in cavity catalysis [13][14][15][16][17][18][19][20][21][22][23][24] – albeit slowly [25] – but have

• electrophile [175]. In terms of polarization, since cages are invariably charged [36], a few MOCs have demonstrated charge stabilization of transition states (Figure 5B). A key example uses the highly successful Raymond gallium-based cages, exploited by Raymond, Bergman and Toste [21][37][107][155][165][168

• triad (red) was hoped to activate the benzyl alcohol nucleophile, but it does not activate (polarize) the electrophile (substrate ester group). (B) One of Rebek’s “clefts” [108][109]. The rigidly organized carboxylic acids both bind the substrate and the transition state for hydrolysis of an acetal. (A

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• 1.0 equiv of 19 were used. Copper-catalyzed asymmetric hydroamidation of vinylarenes. a4 mol % + 2 mol % catalyst was used. b4 mol % + 4 mol % catalyst was used. cSlow addition of the amide electrophile solution. Copper-catalyzed anti-Markovnikov hydroamidation of alkynes. Copper-catalyzed preparation

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• Figure 11. Initially, the Cu(II) catalyst 50 coordinates with substrate 47 and amine electrophile 48 to generate Cu(II) intermediate 51, which is then oxidized by the iodine radical to form Cu(III) complex 52. Cu(III) complex 52 undergoes electron transfer to produce radical cation intermediate 53

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• ring was obtained using the same reaction as previously reported for PHn (Figure 1) [45], between 2,2’-dilithiobiphenyl derivatives but this time with the electrophile decafluorobiphenyl C6F5–C6F5 instead of C6H5–C6F5 (Fn, n = 3–12, Scheme 1). The presence of the terminal fluoroarene group in Fn