Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• intermediate D via intramolecular radical cyclization. A single-electron-transfer (SET) process then occurred between the radical B and the radical D, resulting in the generation of cationic intermediate E, difluoroacetate anion and PhI. Finally, the product 3a was obtained after the deprotonation by

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• isoquinoline ring via gold(I)-mediated 6-endo hydroamination (Scheme 2). Treatment of 11 with a cationic gold complex, generated in situ from AuCl(PPh3) and AgNTf2 [47][48][49][56], with an excess amount of triethylamine in 1,2-dichloroethane at 65 °C, resulted in the intended regiocontrolled hydroamination

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• established methods, including 1H NMR-based hydrogen bond acidity determination, UV–vis spectroscopy titration with Reichardt's dye, and 1H NMR titration using tri-n-butylphosphine oxide as a hydrogen bond acceptor. Our experiments reveal that the direct attachment of the CF2H group to cationic aromatic

• -methylpyridinium cations and related analogs (Figure 2). We anticipated that such cationic constructs would enhance the Brønsted acidity of the CF2–H bond by stabilizing the conjugate base of the CF2H group, in turn, increasing the hydrogen bond donation ability. Additionally, to minimize the effects of

• as the charge of the solute changes, complicating the Δδ-based direct assessment of HB acidity. To quantify the HB donation ability of both neutral and cationic species on a single scale, we chose an alternative strategy based on an established UV–vis spectroscopy titration method [52] with

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• effectively applied to form orthogonal supramolecular polymers. The macrocycle-mediated connectivity was confirmed by single-crystal X-ray diffraction, which revealed a unique 2:2 binding motif between host and guest, bridged by two cationic pyridinium end groups through π-stacking interactions and other

• amide macrocycle with six aromatic residues (hereafter called cyclo[6]aramide for brevity, Scheme 1a) could mediate dimerization as a host. That is because such a 2D macrocycle has six carbonyl oxygen atoms pointing inwards as binding sites, demonstrating excellent affinity for cationic organic guests

• molar ratio observed in ESI experiments. These inspiring results prompted us to further examine the interaction between host H1 and G1 by 1H NMR spectroscopy. Our prior experience with cyclo[6]aramide has confirmed binding to the cationic guest [49]. Indeed, addition of compound H1 to the guest solution

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

• bromine radical attack that leads to the formation of a cationic brominated copper complex 77. Anodic oxidation and subsequent proton transfer provide the desired product 73 and regenerate the copper catalyst. Olefin addition Hydrofunctionalization and difunctionalization of alkenes are valuable methods

• an alkene to generate a radical intermediate, followed by oxidation, which enables radical-polar crossover (RPC) and the subsequent nucleophilic attack of the cationic intermediate [67]. Alternatively, the initial radical intermediate can be trapped by a transition-metal catalyst, followed by a cross

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• , respectively. The latter interacts with the alkene generating an alkyl radical IV that converts to the cationic intermediate V by single-electron oxidation by the Cu(II) species. Finally, the attack of the nucleophile leads to the desired products 6. Starting from aryl carbazates, intermediate II, adds

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• substituted carbon that is more cationic leads to the product. Synthesis of β-fluorinated piperidines 6 with in situ-generated HVI reagent was reported in 2014 by Kita, Shibata and co-workers (Scheme 4) [29]. Using difluoroiodotoluene 10, formed in situ from 4-iodotoluene, pyridine·HF and m-CPBA

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• the distortion/nonplanarity of the macrocycle and the resulting availability of pyrrolic protons is necessary for catalytic activity [61]. A set of 18 different metal-free porphyrins (non-alkylated, neutral alkylated, and cationic alkylated) with varying degrees of distortion from planarity as well as

• an inactive tetraarylporphyrin 18, by increasing the porphyrin basicity and distortion. On the other hand, di-N-alkylation of 18 (providing compound 38) reduced the catalytic activity to only 5% conversion. The authors also screened cationic N-alkylated macrocycles (39–41) and found that only 39 with

• pyrroleninic core of the porphyrin is diprotonated, which induces the formation of supramolecular aggregates, stabilized by ion-pair contacts (electrostatic interactions) between the cationic porphyrin centers and anionic sulfonate groups of the periphery (Figure 10a). In 2018, the group reported heterogeneous

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• properties. Specifically, Qian and co-workers examined 7395 bacterial genomes and identified more than ten thousand potential cationic NRPs. They focused on a few promising candidates after bioinformatic-based dereplication and found two NRPs, brevicidine and laterocidine, that worked in an animal thigh

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• , only a few reports with the focus on host–guest binding studies exist in which classic cationic metal-driven self-assemblies seem to be capable of binding oxalate without suffering from its competitive nature [75][76][77][78][79]. Guest encapsulation was investigated with cationic metalla-rectangles as

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• radical–Ru(III)(OH) intermediate, which provides the cationic intermediate from phenol via electron transfer. The reaction of cation D with TBHP results in the mixed peroxide 87 [84]. However, this mechanism was later doubted based on the experimental data of [Rh2(cap)4]-catalyzed peroxidation of phenols

• catalytic cycle. A Pd-catalyzed synthesis of di-tert-butylperoxyoxoindole derivatives 210 from acrylic acid anilides 209 and TBHP was developed (Scheme 65) [134]. The authors proposed that the initially formed diperoxide A undergoes electrophilic attack by cationic Pd(II) on an aromatic C–H bond with the

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• in aryl-transfer processes, DIAS are frequently employed as photoinitiators for cationic polymerizations [31][32][33], Lewis acids [34], oxidants [35][36] and in the field of macromolecular chemistry [37][38]. Additionally, biological activity is also exhibited by iodonium salts, often due to their

• intramolecular. In the presence of a base, the triflate anion is extracted, forming a cationic trifluoromethanesulfonyl group as an intermediate. Thus, the products are believed to form via a sulfonyl-directed nucleophilic aromatic substitution pathway. Finally, the products are obtained through the dissociation

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• molecule on this cation, followed by tautomerism (path a). The intramolecular attack of an amide carbonyl on this cationic site in intermediate 10, leading to the formation of oxonium ion 11, is also possible (path b). After the addition of water, the formed hemiacetal 12 was hydrolyzed to give the

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• , respectively. In this study, by mimicking our previous system of triad molecules and living cells, we report a simplified model system with a cationic C60 derivative (catC60) and a liposome with embedded 1-pyrenebutyric acid (PyBA) to demonstrate that the addition of PyBA was important to achieve fast and

• ) liposomes of 1,2-dimyristoyl-sn-glyreco-3-phosphocholine (DMPC, Figure 1d), a well-known model of the plasma membrane, (ii) a cationic derivative of C60 (catC60, Figure 1e) as a replacement of the triad molecules, and (iii) 1-pyrenebutyric acid (PyBA, Figure 1f) as an anchor molecule for catC60 to be

• present study for controlling both the location and photodynamic actions of a cationic derivative of C60 (catC60), a simple model compound of the triad molecules, in a membrane via π–π interactions with 1-pyrenebutyric acid (PyBA). (d–f) Chemical structures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• synthesized to investigate the interactions for the bulky cation. Single-crystal X-ray analysis of the TATA+ ion pairs revealed solid-state ion-pairing assemblies without stacking at the cationic π-planes. The TATA+ cation showed counteranion-dependent assembly structures, with smaller counteranions located

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• corresponding 1,2,4-triazolium tetrafluoroborates under electrochemical conditions [29]. The reaction is conducted with a stoichiometric amount of HBF4, which converts the substrate to the corresponding cationic intermediate via a protonation, eliminating the need for an additional supporting electrolyte. The

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• limitation, we analyzed the mechanism underlying the formation of resorcin[n]arenes. The first step of the cyclization reaction is a hydroxyalkylation involving various cationic intermediates [69]. Hence, we hypothesized that any factor enhancing the rate of the first step by stabilizing carbocations will

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• the diastereoselectivity of the nucleophilic attack of the β-lactam on the radical cationic intermediate was influenced by stereoelectronic factors. Compounds unsubstituted at position C-3 of the β-lactam ring, 11d–h, showed modest stereoselectivity with a higher dr (6.7:1) for compound 11d, which has

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• = 10.9139(1) Å, c = 24.3668(3) Å, β = 95.601(1)°) and a density of 2.01865 g/cm3. Two units of the cationic XB donor form a dimer, which is bridged via two bromide ions (Figure 2). As usual for DAI salts, two XB axes are found on the elongations of the C–I bonds. On the one trans to the isoxazolium unit

• , indicating that the activated gold complex is the catalytically active species. Furthermore, stability measurements (1H and 19F NMR) of 1:1 mixtures of the gold complex and the XB donors were performed in order to investigate the stability of the cationic iodonium structures towards the gold complex [28

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• corresponding free amines by hydrolysis with aqueous HCl. The reaction proceeded in good yields and with complete retention of stereointegrity. In a proposed mechanism, isatin carbonate 137 reacts with a quinuclidine unit of the catalyst 138 by an SN2’ attack to form cationic intermediate 142. The t-BuO− anion

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• recently developed a metal-free aziridination of unactivated olefins via the intermediacy of an N-pyridinium iminoiodinane (Scheme 1b) [34]. We rationalized the enhanced reactivity towards olefin aziridination as a result of charge-enhanced iodine-centered electrophilicity arising from the cationic N

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• brilliance of synchrotron X-ray sources enables the mechanisms of structural changes in PS to be studied, using in-situ light irradiation with time-resolved data collection. For example, Tribet and co-workers used this approach to explore the kinetics of micellisation and dissolution of cationic Azo-PS, both

• that ensure the Z-rich PSS can be measured appropriately. To address this, here we investigate the effects of light- and X-ray irradiation on PS assemblies to further understand the parameters which influence X-ray-induced Z–E isomerisation. Two different cationic PS molecules are studied, based on the

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• the electrolysis was a four-electron oxidative process. Based on this study, the authors proposed the initial anodic oxidation of hydrazone 44 through the loss of two electrons and one proton to form cation 47. Subsequent nucleophilic addition of the azaarene led to new highly acidic cationic species

• iodonium through a two-electron process. Subsequent reaction with the hydrazone and deprotonation formed the N-iodo hydrazone intermediate 80, triggering the reaction with the amine 78 through cationic species 81. Final cyclization delivered the desired pyrazole 79 (Scheme 15) [60]. The group of D. Tang

• ) atom were well tolerated and the best result was obtained with a morpholine ring. Based on cyclic voltammetry studies, the transformation initiated with the anodic oxidation of hydrazone 101 to form highly electrophilic radical cationic species 104. Subsequent addition of azide 102 and desilylation