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

• , chemists have made use of selectively reactive chemicals by handling them, individually, in unreactive bottles. Meanwhile, Nature has learned to convert mixtures of unreactive chemicals by handling them in selectively reactive bottles (enzymes). Only the latter approach offers the efficiency, rate

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• to weak antimicrobial efficiency against E. coli, and C. albicans (see Figure S43 in Supporting Information File 1). These experiments showed that compounds 7b and 7h have potential antistaphylococcal activity. Microbroth dilution assays [52] were performed for the determination of MIC (minimum

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• states. In this section, the document highlights applications of these complexes in reactions like ring-closing metathesis and polymerization, where red light’s deeper penetration enhances yields and efficiency, particularly for large-scale reactions. The second section broadens the focus to explore

• efficiency of photoredox-catalyzed reactions. Absorption in the red region opens up innovative opportunities for photochemical transformations. First, the employed photon has the lowest energy in the electromagnetic spectrum of visible light, which allows for safer laboratory conditions in terms of

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• convergent chemistry characterized by diversity, complexity and efficiency. MCRs are compatible with C1 chemistry due to the generally great tolerance of different functional groups. They have been mostly employed in the synthesis of oxazolidinones and oxazinanones utilizing CO2 and CO [4][16][17][18][19][20

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

• motifs such as a benzofuran, indazole, and quinoline were also shown to undergo the desired Markovnikov amidation with high efficiency (23j–l). Several mechanistic experiments were performed to rationalize the reaction pathways. As shown in Figure 7, copper hydride, generated from a copper precatalyst

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

• functionalization of highly complex and diverse molecules, such as those of pharmaceuticals and natural products, has provided new retrosynthetic disconnections for complex compounds, contributing to improved resource efficiency [41][42][43][44][45][46]. Recently, the merging of C–H activation and electrochemistry

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

• , also in regio- and stereoselective processes. The interest for these strategies arises from the cost-effectiveness as one-pot processes, the ease of application and the great efficiency when directed to the synthesis of biologically active compounds. Plausible general catalytic activation for ionic or

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

• (Scheme 61) [91]. After testing a considerable number of substrates, the authors achieved excellent yields and enantioselectivities. The synthetic utility of this approach stems from being able to skip additional reaction steps and thus omit reagents used in those steps, leading to increased efficiency

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• selection, a dispensing module for solids and liquids, a reaction module capable of heating and stirring, a sample preparation module, and a LC–MS characterization module (Figure 2d). The efficiency of the system has been demonstrated in three reactions types, namely Suzuki–Miyaura coupling, Buchwald

• –Hartwig amination, and Ullmann coupling. These experiments showcased a conversion rate that outperformed existing reference systems and provided at least six times the efficiency in the experimentation, besides synthesis planning, optimization, and downstream workup tasks. The throughput of SynBot is

• , differing from established isolation and separation techniques, holds the promise of not only enhancing the efficiency of HTE flow synthesis but also paving the way for more sustainable growth in this research area. Autonomous self-optimizing flow reactors Autonomous self-optimizing flow reactors (ASFRs

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• electrochemical studies, showing that the photophysical properties of PhFlOP depend on the nature of the electron-donating groups [31]. Later, Wu and co-workers introduced various electron donors to the PhFlOP unit to form new TADF emitters with high electroluminescence efficiency [32][33]. Despite this progress

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

• formed by carboxylic acids, enhancing its versatility and effectiveness in drug design [27]. Traditional sulfonamide preparation involves combining sulfonyl chlorides and amines [25][28][29]. Despite the efficiency of traditional methods, challenges still remain, e.g., use of harsh conditions, like

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• dehydropiperazic acid to act as β or γ-turn is excluded. Interestingly, this novel scaffold rather promotes extended structures. Conclusion To conclude, we have developed a new methodology to synthesize β-analogs of dehydropiperazic acid incorporating fluorinated groups. In order to improve the efficiency of this

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

• three or more reagents are combined in one step to yield a single product that contains most of the atoms from the starting materials [1][2]. Among the advantages of MCRs are their high atom economy and efficiency in bond formation, along with the cost-effectiveness of separating and purifying products

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

• , Xu, Zhang, Zhu and co-workers reported a method to catalytically synthesise 5‑fluoro-2-aryloxazolines 39 by utilising BF3·Et2O as the fluoride source and activating reagent (Scheme 21) [6]. The synthesis of these derivatives was achieved with high efficiency, resulting in good to excellent yields of

• reaction of 2-alkenylanilines 65 with PIDA and LiBr resulted in the successful synthesis of various 3-bromoindoles 66 in high yields obtained under the optimised reaction conditions, highlighting the efficiency of the synthetic protocol. The proposed mechanism suggests that the reactive AcO–Br species is

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• efficiency and creating six new bonds (two C–C, three C–N, and one N–N). Additionally, the products were evaluated against breast cancer MCF-7 cells, finding moderate activity in the compounds substituted with fluorine and chlorine. Keywords: 1,5-disubstituted tetrazoles; high-order multicomponent reaction

• -disubstituted tetrazole-methanesulfonylindole derivatives, with yields ranging from 16% to 55% after purification by column chromatography. Despite some yields being modest, they are deemed reasonable considering the reaction’s structural complexity, atom economy, and the efficiency achieved in terms of time

• . Significantly, this protocol enables the rapid and straightforward synthesis of highly 2-substituted indoles with high bond-forming efficiency, creating six new bonds (two C–C, three C–N, and one N–N). Our synthetic strategy would represent the second report in which the Pd/Cu-catalyzed heteroannulation

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

• ). Indeed, the quenching efficiency of triplet-excited [Ru(phen)3](PF6)2 by 1i was calculated to be as low as 5% under the highly diluted conditions required for the experiments in Figure 3. In order to gain structural information about the photoproducts, the photoisomerization reactions were also examined

• be investigated in the presence of the photosensitizer because these substrates have no sufficient solubility in acetonitrile. To assess the efficiency of the photoreactions, photoisomerization quantum yields were determined in cyclohexane by actinometry (λex = 310 nm or 340 nm) [41][42]. The quantum

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• flexibility, high efficiency, and versatility, making them essential for modern high-tech applications. Despite the wide variety of known push–pull molecules, the number of fluorescent cores with synthetic potential for tuning the emission wavelength to achieve a full-emission spectrum is limited. Typically

• rigidity along the C–C bond between the heterocycle and ethene bridge due to the fused cyclic fragment. As a consequence of the additional ring, the fluorescence efficiency increased. At the same time, solid-state emission was observed due to the steric hindrance, which prevented intermolecular

• highest fluorescence efficiency of 53.4% was observed for the para-methyl derivative 1b. Solutions of stilbazoles 1 in DMSO were also characterized by large Stokes shift values, reaching 207 nm (5846 cm−1) and showing nonradiative loss of excitation energy. It should be noted that stilbazoles 1, in

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• transfer and increases the efficiency [12]. Three conditions should be met for the target porphyrins of this study. 1. The acid covalently bound to the porphyrin should have an acid strength similar to trifluoroacetic acid. 2. The length of the tether with which the acid group is bound should be sufficient

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• × 10−4 cm2 V−1 s−1) and 2-ethylhexyl chains (4.93 × 10−5 cm2 V−1 s−1). The stronger π–π interactions led to a higher power conversion efficiency (PCE) as a result of the higher short-circuit current density (Jsc), due to films with higher crystallinity providing a smoother pathway to charge carriers to

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

• , diaryliodonium salts (DAIS), a versatile category of hypervalent iodine compounds, have seen significant progress in hypervalent iodine chemistry. Their efficiency and environmentally friendly characteristics have positioned DAIS as next-generation arylation reagents [29][30]. Other than aromatic electrophiles

• efficiency and effectiveness as a synthetic approach. Furthermore, a transition-metal-free arylation of quinoxalines 17 and quinoxalinones 19 via aryl radicals was discussed by Li and co-workers in 2022. In this report the aryl radicals were generated by planetary ball milling of diaryliodonium salts 16 at a

• . Notably, the efficiency of the cross-coupling reaction was observed to increase with the transfer of electron-poor aryl groups from the hypervalent iodine salt. Thus, electron-withdrawing substituents such as trifluoromethyl, m-chloro, and fluorine on the aryl group promoted efficient coupling. Moreover

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

• achieve this goal [7][33]. Among them, isocyanide-based multicomponent reactions (I-MCRs) are one of the well-known strategies in this field due to their operational simplicity, one-pot, convergent properties and atom economy, high efficiency, and high levels of chemical selectivity [34][35][36]. In

• increase and the electron-donating substituents led to a decrease in the reaction efficiency (Scheme 3, 4a–k). In addition, benzothiazepine was used in this protocol and the corresponding pyrrole-fused benzothiazepine was obtained with a yield of 73% (Scheme 3, 4l). Also, various isocyanides were suitable

• benzoxazepine, the presence of an electron-withdrawing group leads to an increase in the yield of pyrrole-fused triazolobenzodiazepines whereas electron-donating groups led to a decrease in its yield. Also, the substitution of naphthyl used in gem-diactivated olefins increased the efficiency of the desired

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched

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

• efficiently converted to the target products under solvent-free conditions. The reactions proceed at room temperature and are complete within 90 minutes, demonstrating both efficiency and experimental simplicity. Keywords: ball milling; difluorocarbene; difluoromethylations; difluoromethyl enol ether

• reaction conditions with difluorocarbene precursor 2, KFHF (4 equiv) as activator, and CsCl or KCl (4 equiv) as grinding auxiliaries in a PTFE milling jar for 90 min at 25 Hz (Scheme 3). To get an initial efficiency estimate, the crude reaction mixtures were first analyzed by quantitative 1H NMR

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• high enantiomeric excess (90% ee for (S)-23d and (S)-23e). Furthermore, it was found that the substituent position on the aromatic ring did not significantly influence the reaction efficiency as well as optical purity and the reaction proceeded in a highly enantioselective manner (91% ee for (S)-23f