Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• conducted on a Cary 5000 spectrophotometer. A C3 epsilon potentiostat from BASi was used for the electrolysis using a thin layer cell from a demountable Specac® Omni cell. In this cell, a three-electrode system was coupled to conduct in situ spectroelectrochemistry. A Pt gauze and a Pt wire were used as

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• role in most cases is to generate highly reactive species in situ from the nucleophilic reaction component. This can subsequently interact with other reaction components to form target products. Compared to the crotonic condensation products of other aliphatic and aromatic aldehydes, methylidene

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

• reaction involves an in situ generation of the iminium cation A followed by isomerization to the thermodynamically more stable iminium cation B. Subsequent nucleophilic attack of a copper acetylide enabled regioselective C–C bond formation at the C11 position. After removal of the cyclic acetal, the

• 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

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

• esters containing a quaternary stereocenter, and the control of regioselectivity depended on the bulkiness of the substrates. Additionally, the electrochemical system served as an internal syringe pump, generating quinone from hydroquinone in situ through anodic oxidation, which enhanced the

• performed using electrophilic chlorinating reagents or stable and readily available chloride sources with stoichiometric amounts of chemical oxidants. However, in this catalytic system, chloride (Cl−) from HCl was used as the chlorinating agent, and electrophilic chlorine (Cl+) was generated in situ by the

• enantio-determining transition states. Based on the mechanistic studies, a reaction mechanism is proposed in Figure 14. First, the in situ-generated Cu(I)–CN complex 83 is oxidized at the anode to form a Cu(II)–CN complex 84, which reacts with diarylphosphine oxide 80 to generate a transient P-centered

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

• involves a Friedel–Crafts alkylation of the arene followed by hydroamination (Scheme 6) [5]. The mechanism plausibly starts with the in situ formation of triflic acid from Cu(OTf)2 which leads to protonation of the oxygen atom of the alcohol with generation of the activated allyl alcohol. This latter gives

• ]. Three-component coupling of amines, aldehydes or ketones, and terminal alkynes catalyzed by Cu(OTf)2 is a fruitful tool for the production of α-substituted propargylamines 10 (Scheme 7) [20]. The reaction involves the alkynylation of the corresponding imines formed in situ and provides higher yields

• (Scheme 16) [33]. The reaction, which occurs with formation of C–C, C–N and C–O bonds, involves a nucleophilic addition of the activated alkyne XIV to the in situ-generated iminium ion XV, followed by cyclization to form a quinoxalin-2-one intermediate XVI. A subsequent 5-endo-dig cyclization involving

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

• be carried out in a one-pot fashion with comparable results and without significant variation from the two-step procedure. Utilization of the Povarov reaction and subsequent oxidation by DDQ was also done by Wang et al. in 2020 [54]. In situ-formed imines from anilines 91 and benzaldehydes 92 were

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• reagents (HIRs) bearing a benzylamine with in situ-generated sulfenate salts was investigated. Under the studied conditions sulfonamides have been obtained in up to 52% yield. This reaction has been extended to a variety of HIRs and sulfenate salts to explore the different reactivity of these new reagents

• benziodoxolone was generated in situ, via a reaction of chlorobenziodoxolone with sulfinate salts, followed by the addition of amines or hydrazines, respectively. On the follow-up on our research, we envisaged to extend the diversity of BBX reagents as electrophilic amine reagents and investigated their

• reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals

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

• , prepared in situ from the reaction between 3,3’,4,4’-tetra(alkoxy)-2,2’-dibromo-1,1’-biphenyl, 2Br-BPn, and n-BuLi at low temperature. All new Fn compounds were prepared as previously described by reaction of 2Li-BPn with decafluorobiphenyl, C6F5-C6F5 (Scheme 1). The starting materials 2Br-BPn were

• derivatives: the in situ prepared 2Li-BP5/6 was reacted with F5/6 to yield the symmetrical discotic dimers, G55/G66 respectively, in an average yield of 42–45% (Scheme 1). The reaction of 2Li-BP8 with F4 was also successfully tested, and allowed the preparation of the unsymmetrical discotic dimer G48

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

• reaction takes place (Scheme 17). In 2020, He, Yang and co-workers reported a phosphoric acid-catalyzed enantioselective inverse electron demand aza-Diels–Alder reaction of in situ-generated β,β-disubstituted α,β-unsaturated N–H ketimines and azlactones [42]. This methodology enabled the synthesis of

• : the azlactone is activated by the chiral phosphoric acid to generate its active enol form, while at the same time the chiral phosphoric acid mediates the in situ formation of the α,β-unsaturated N–H ketimine, occurring through the formation of an orthoester intermediate A. Then, the chiral phosphoric

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• converted to a mechanistically-required Cu(I) species in situ through the addition of a reductant (e.g., sodium ascorbate, NaAsc) [31][32], or via Glaser–Hay alkyne homocoupling [33][34]. The mild and accessible nature of the CuAAC reaction has allowed the use of azide or alkyne components that bear

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• obtain α-acylaminoamides. Innovation in recent years with alternative reagents, like N-hydroxyimides or nitric acid in place of an acid, N-alkylated hydrazines, or nitrobenzene derivatives (reduced in situ to anilines) instead of amines, and in situ-prepared isocyanides, makes it a versatile method for

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

• to form an iodonium species. Nucleophilic attack occurs on the least hindered carbon of the iodonium, before displacement of the HVI by fluoride to give the product. Zhang and co-workers reported the intramolecular aminofluorination of unsaturated amines using an HVI reagent generated in situ from

• difluoroiodobenzene 10 is formed in situ, which is activated by HF. Two possible mechanisms were given for the synthesis of pyrrolidines 14, which are the same two proposed for the synthesis of piperidines 6 (Scheme 1). Either an alkene-activated iodonium is formed or an activated electrophilic nitrogen is generated

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

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• corresponding quadricyclanes [24][29][30][34]. As the photometric analysis of the photosensitized reaction of 1i and 1l pointed to a relatively clean and robust reaction, the irradiation of 1i in the presence of [Ru(phen)3](PF6)2 at λex = 520 nm was additionally monitored by in situ NMR spectroscopy [40

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

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

• generate the nucleophilic carbon radical B. The intramolecular 1,5-HAT of B provided the alkyl radical C, which then cross-coupled with the in situ-generated high-valent Mnn+1OO-t-Bu species to form the 1,6-difunctionalized product 42 via peroxy-ligand transfer. The remote trifluoromethylthiolation

• in situ-generated Cu(I) complexes was developed (Scheme 23) [43]. 2-Phenylbutane (64) was converted into peroxide 65 in a 70% yield with 4% ee. A visible light-induced direct decarboxylative peroxidation of carboxylic acids 66 with the formation of peroxides 67 under metal-free conditions using Mes

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

• . A synthetic protocol for diaryl ethers via an in situ generation of a hypervalent iodine salt was introduced by Stuart and co-workers in 2020. To study the scope of the reaction first various substituted aryl(TMP)iodonium salts 12 were reacted with different substituted phenols 61 in the presence of

• 62, starting with aryl iodides and phenols 61. In this metal-free reaction, aryl(TMP)iodonium salts 12 were prepared in situ from aryl iodides via treatment with m-CPBA, TsOH, and TMB at 55 °C in acetonitrile, which subsequently react with the substituted phenols 61 to produce the O-arylated products

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• . developed a method to access thiocyanated derivatives including an aldehyde hydrazone (a unique example) in 70% yield thanks to the in situ generation of SCN-succinimide from NCS and NH4SCN (Scheme 1) [67]. In the same vein, the group of Monteiro [68], then Hajra [69], independently, reported the synthesis

• of 5-thioxo-1,2,4-triazolium inner salts by the nucleophilic thiocyanation of N,N-dialkylhydrazonoyl bromides, in situ generated from aldehyde-derived hydrazones in the presence of an oxidant (NBS, (NH4)2S2O8), Scheme 1). In 2024, the synthesis of 2‑imino-1,3,4-thiadiazoles was achieved by

• transformation, experiments with different SCF3 sources were conducted. First, we hypothesized that trifluoromethylthiolated succinimide, which might be in situ generated from NBS and AgSCF3, could be the active species. When the reaction was carried out in the presence of this electrophilic source and 1a, no

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• with 1,10-phenanthroline as cyclic imine under solvent-free conditions for the synthesis of pyrrole-fused phenanthroline. This reaction proceeds via in situ formation of zwitterion I through reaction of the aldehyde and malononitrile followed by 1,3-dipolar cycloaddition (Scheme 1a) [41]. Chen and co

• -workers reported a one-pot three-component reaction (3-CR) of sulfamate‐derived cyclic imine, isocyanide, and acetylenedicarboxylate. In this reaction too, the pyrrole-fused sulfamate is synthesized through intermediacy of the in situ-formed zwitterion II and [1 + 2 + 2] annulation reaction (Scheme 1b

• ) [42][43]. Another I-MCR for forming pyrroles is the in situ formation reaction of the zwitterion III, known as Huisgens 1,4-dipole. The latter is formed by the reaction of imines with acetylenedicarboxylates and can be trapped by an isocyanide through a [4 + 1] cyclization reaction to synthesize

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• with TMS-protected ᴅ-glucosyl iodide, generated in situ by reaction of penta-O-trimethylsilyl-ᴅ-glucose (6b) afforded indigo-N-α-ᴅ-glucoside 7d, albeit, in low yield (Scheme 10) [21]. The reaction of 13 with TMS-protected ᴅ-mannosyl iodide, generated in situ by reaction of penta-O-trimethylsilyl-ᴅ

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

• ,O-acetal derived from diethyl mesoxalate (DEMO) undergoes elimination of acetic acid upon treatment with a base, leading to the formation of N-acylimine in situ. Lithium acetylide readily attacks the imino group to afford N,1,1-tricarbonylated propargylamines. When the resulting propargylamine

• anhydride, the intermediately formed hemiacetal underwent acetylation, leading to N,O-acetals 1. In this method, an acid amide can be used as an amine masked with an acyl group. Subsequent elimination of acetic acid occurred to afford 2 in situ upon treatment with a base, enabling nucleophilic addition with

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• each addition. In situ preparation of the [Tb.1·3Cu]3+ sensor. Solutions of 5 μM [Tb.1·3Cu]3+ were prepared by combining a DMSO stock solution of Tb.1 (100 μM) with 1 mM Cu(NO3)2·5H2O(aq). Solutions were then diluted with the appropriate amount of buffer (final concentration 10 mM Tris–HCl or 10 mM

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• hemisulfate to its basic form in situ. Thin-layer chromatography (TLC) and high-performance liquid chromatography with mass-spectrometric detection (HPLC–MS) were used to monitor the reaction and to identify the products obtained. It should be noted that in the case of HPLC–MS analysis, the signals registered

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• Jinbo Ke Pit van Bonn Carsten Bolm Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.20.235 Abstract We present a mechanochemical synthesis of difluoromethyl enol ethers. Utilizing an in situ generation of difluorocarbenes, ketones are

• isolating the low-boiling non-polar products. Mechanistic studies suggested that in situ-generated difluorocarbene reacts with the ketone oxygen, followed by intermolecular protonation/deprotonation. Although the process has still synthetic limitations, also acyclic ketones can now be converted into

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• , our plan provides: the oxidation of N-aryltetrahydroisoquinolines (N-Ar-THIQs) generating in situ the iminium ions 1, the 3C Ugi-type reaction of an electron-rich aniline, an isocyanide and 1; the subsequent oxidation of the Ugi-type product 2; and the final cyclization to give the spiro[indole-THIQs

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• developed. NMR studies confirmed the role of in-situ-generated hydroperoxide in the conversion. The protocol was applied to a diverse range of substrates to access the target products in good to excellent yields. A structure–activity study for the 5-substituted-2-hydroxybenzophenones towards UV-protection

• protocol using a hydroperoxide (Figure 2d) gave us an idea that the use of an in-situ-generated hydroperoxide may trigger the reaction, and may avoid the use of transition metal in the reaction. Many solvents, e.g., tetrahydrofuran (THF), dioxanes etc. are known for producing hydroperoxides in situ on long

• , after getting the best yield of the product using Cs2CO3, we changed the solvent to dichloromethane, 1,4-dioxane, and acetonitrile. Except for 1,4-dioxane (Table 1, entries 18–20), where hydroperoxide is known to be produced in situ, the yields were very low. However, the reaction in 1,4-dioxane took a