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

• fluorescent protein (GFP), has revolutionized genetics by providing highly accurate real-time detection of fusion proteins in vitro and in vivo [1]. Pioneering work on GFP-tagged proteins for real-time monitoring of gene expression was first reported by Chalfie and co-workers in 1994 [2]. For a long time

• better solubility in the reaction buffer and did not require DMSO as co-solvent, making it a very promising candidate for in vivo applications. To complete the study, and given that the mesyloxy group has shown superior efficacy over all other functional groups tested for Pepper alkylation, we

• (left side). Bar graph (right side) illustrating the relative yields of covalent tethering under the following conditions: 2.5 µM RNA, 50 µM HBC ligand, 100 mM KCl, 2 mM MgCl2, 50 mM HEPES buffer, pH 7.0, 5 h at 37 °C. The numbers in the orange bars indicate the percentage of DMSO (%) used as co-solvent

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• (CHE-1807486) for past financial support. We thank the National Institute of General Medical Sciences of the National Institutes of Health (R35GM153362) for current financial support of this project. Conflict of Interest L.I. is co-founder and holds equity in Reversal Therapeutics (National Harbor

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

• organolithium species and the other employing chiral organoboron compounds. Copper-mediated stereospecific coupling of chiral organolithium species with allylic electrophiles In the organolithium approach, a breakthrough was achieved by Knochel and co-workers through carefully controlled reaction conditions

• stereochemical integrity. Through these careful experimental controls, Knochel and co-workers effectively addressed the long-standing challenge of handling these traditionally unstable chiral organometallic intermediates. Copper-catalyzed stereospecific coupling of chiral organoboron species with allylic

• configurationally stable organoboron compounds was recently developed by Morken and co-workers, which employs only catalytic amounts of copper [47][48]. Their strategy uses chiral secondary organoboron compounds 20 as precursors to generate chiral alkylcopper species through a carefully controlled activation and

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

• between 60–95% for all metal catalysis conditions. The most widely accepted mechanism is as follows: the alkynyl C–H bond is activated by the metal catalyst (Scheme 23). The metal can be added in its proper oxidation state (such as Cu(I)) or generated in situ (as in the case of Au(I), Co(I), Fe(II) and Ni

• (I)) by reducing the suitable salts (containing Au(III), Co(II), Fe(III), and Ni(II), respectively) at the beginning of the catalytic cycle. The metal in its reduced species (depicted in Scheme 23) activates the C–H bond of the alkyne. After this activation step, a weak base (like DBU, TMG, or even

• afford propargyl halide C. Finally, intermediate C reacts with the secondary amine to give the propargylamine product D. As outlined in the catalytic cycle, the presence of a base plays a dual role: co-activation of the alkynyl C–H bond through deprotonation and trapping of the HCl produced during the

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• organic chemistry [2][3][4][5], organocatalysis [6][7], metal catalysis [8][9], biochemistry [10][11], materials science [12][13], and supramolecular chemistry [14][15], although its successful application to asymmetric catalysis has been limited (Figure 1) [16][17][18][19][20]. In 2018, Arai and co

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

• , which provided the products in high yields with up to 33% ee [19]. In 2023, García Mancheño and co-workers reported the tetrakis(iodotriazole) 3-catalyzed dearomatization of halogen-substituted pyridines 4, which formed the corresponding products 5 in high yields with up to 90% ee (Figure 1b) [20

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• Long K. San Sebastian Balser Brian J. Reeves Tyler T. Clikeman Yu-Sheng Chen Steven H. Strauss Olga V. Boltalina Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA ChemMatCARS, University of Chicago Advanced Photon Source, Argonne, IL 60439, USA 10.3762/bjoc.21.39

• , allows a tentative conclusion that photooxidation proceeds via dearomatization of the central ring due to the formation of the endoperoxide (Figure 4). This suggestion is also supported by a recent work of Sun and co-workers where they observed and structurally characterized the endoperoxide of 9,10-ANTH

• (trifluoromethyl)benzene (1,4-C6H4(CF3)2, Central Glass Co., 99%); dimethyl sulfoxide (DMSO, Fisher Scientific, ACS grade); anhydrous magnesium sulfate (MgSO4, Fisher Scientific); Cu powder (Strem Chemicals, 99%); dichloromethane (EMD Chemicals, ACS grade); acetone (technical grade); THF (Aldrich/Merck, ACS grade

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• solid state, which are highly dependent on molecular packing. The concept of topochemical reactions was first introduced by Kohlschütter in 1919 [1], and topochemical polymerizations were systematically studied by Schmidt and co-workers in the 1960s and 1970s [2][3][4]. Schmidt's pioneering work

• . Experimental Synthesis The studied bimanes were synthesized following the approach reported by Kosower and co-workers [17][19], and an alternative chlorination method developed by Neogi et al. [31]. The synthetic details can be found in Supporting Information File 1. Compounds were crystallized from a MeOH–DCM

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

• 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

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting

• ] using 20 mol % of catalyst A and 20 mol % of p-nitrobenzoic acid (PNBA) as co-catalyst in different solvents at room temperature. The results obtained are summarized in Scheme 3 and Table 1. The progress of the reaction was monitored using thin-layer chromatography (TLC) and 1H NMR analysis of the

• provide the highest enantiomeric ratio. The influence of catalyst, co-catalyst, and temperature on the reaction progress and enantioselectivity was further investigated. Different essays using 0.028 M toluene solutions were carried out, and the results are summarized in Table 2. The reaction also occurs

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• grinding serves to dissociate the more loosely bound 2.3 from 2.2, where a release of strain energy and formation of a more thermodynamically stable 2.1·2.2 complex for a subsequent turnover are favored. The first preparative example of photomechanochemistry via manual grinding was reported by Wang and co

• % yield, albeit after 72 h of irradiation. This experiment proved that 4.2 can be used in a sub-stoichiometric way, in fact acting as a catalyst. More recently, based on their previous approach via manual grinding (Scheme 2) [64], MacGillivray and co-workers adopted the vortex grinding method to enable

• exposing fresh material to light. In 2016, König and co-workers exploited rod milling to develop a photomechanochemical approach for the riboflavin tetraacetate (RFTA)-catalyzed photocatalytic oxidation of alcohols to the corresponding carbonyl compounds upon irradiation with five LEDs (λ = 455 nm) [69

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• -[1,1'-biphenyl]-2-amines 3 with sodium nitrite and an acid under aqueous conditions. Recently, Wencel-Delord and co-workers disclosed an improved protocol toward diazonium intermediates 2 under non-aqueous conditions (t-BuONO and MsOH in acetonitrile) [4]. Nevertheless, the improved method still

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

• therefore can be subjected to automated and high-throughput crystallization studies and, with Szczypiński, Slater, Cooper and co-workers, we were able to isolate all five calculated lowest-energy conformers of cage 1 in the solid state (see crystal cavity heights marked under conformers in Figure 9A) [40

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• computed to characterize the optimized structures as minima (zero imaginary frequencies). Aromaticity was first evaluated by means of the nucleus-independent chemical shift (NICS) [12][69][70][71], proposed by Schleyer and co-workers as a magnetic descriptor of aromaticity. NICS is defined as the negative

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• impurity generated in this process. Nucleophilic acyl substitution competes with aromatic substitution to displace glutarimide and gives a byproduct that can co-elute with the desired product on HPLC throughout the remainder of the synthesis. Scavenging with taurine is a convenient way to minimize this

• confirmed the presence of 6 that similarly co-eluted with 3 and 7 that completely overlapped with 4 on HPLC under our standard conditions (MeCN/0.1% TFA in water, 10%→60% 0→7 min, 60%→100% 7→10 min, 100% 10→15 min) (Figure 3). The identity of these impurities was further confirmed by independent synthesis

• by which glutarimide displacement affects quality control analysis, we tested a series of amines and compared the retention times of 8 and 9 (Table 1). Rather surprisingly, the length of amino-PEG-OH had no effect on the relative retention time of 8 and 9. The byproduct co-eluted with the desired

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

• pairs in glycosylation mechanisms was first reported by Rhind-Tutt and Vernon [44], and later reiterated by various authors, including the seminal graphical analysis of Lemieux and co-workers [45][46][47]. Thus, complete categorisation of the reaction in either of the subdomains of substitution reaction

• is not only difficult but is also defective in principle. This dynamic continuum has also been depicted by an elaborate computational simulation report by Fu et al. in 2021 [41] which was a major follow-up of the work by Crich and co-workers in 2018 [29]. In general cases, the axial glycosides also

• -(benzoyloxymethyl)benzoyl [89] and 2-[(tert-butyldiphenylsilyloxy)methyl]benzoyl [90] among others. Sekine and co-workers developed the 2-(azidomethyl)benzoyl (AZMB) group for protecting the hydroxy groups and the exo-amino functionality of the nucleosides [91]. Despite their disarming nature, Iadonisi et al

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

• [9]. Pyrazolobenzothiazines have also been synthesized and explored as p38α MAPK inhibitors [35]. In 2015, Sabatini and co-workers synthesized a novel series of pyrazolobenzothiazines and identified as new generation anti-inflammatory agents. Two of these compounds are reported with an IC50 of 0.5 µM

• oxygen atom [50]. Preferential N-alkylation (over O-alkylation) of 1,2-benzothiazine scaffolds has also been carried out by Ahmad and co-workers in 2014 and Szczęśniak-Sięga and companions in 2018 [37][51]. Structure elucidation of all the synthesized derivatives was carried out using 1H, 13C NMR, and

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

• also been reported as model systems to investigate redox charged species experiencing evolutions from neutral non-aromatic, to antiaromatic, and to aromatic structures. Xia and co-workers recently reported a modular method to synthesize molecules containing cyclobutadienoid (CBD) groups [18][19][20

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• facile access to BPP was reported by Amsharov and co-workers through the so-called "dehydrative π-extension (DPEX)” reaction [12]. However, functionalized derivatives of BPP have scarcely been explored in comparison to the extensive studies on the derivatives of other PAHs, such as pyrene [15][16][17

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• and predict the thermal reactivity of T-type molecules, and many researchers have made their efforts to control the thermal reactivity in various molecular systems by performing chemical modifications on the molecular structures [46][47][48]. For instance, Aprahamian and co-workers reported that

• replacing the rotor pyridyl group of a hydrazone switch with a phenyl group afforded long-lived negative photochromic compounds [49]. In addition, Hecht and co-workers reported that the thermal stability of indigos can be tuned by N-functionalization [50][51]. They revealed that the introduction of electron

• push–pull derivatives bearing electron-donating and electron-withdrawing groups at the para-position of the benzene rings are known to exhibit very fast thermal isomerizations [53]. Velasco and co-workers also reported that a pyrimidine-based azophenol exhibits thermal back reaction on the nanosecond

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

• groups have reported the direct difluoromethylation/cyclization reaction of benzimidazoles with alkenes for the syntheses of difluoromethylated tricyclic benzimidazoles to date. For example, in 2023, Chen and co-workers pioneered an electrochemical approach for the difluoromethylation and cyclization

• 2019, Gouverneur and co-workers reported a hydrodifluoromethylation of unactivated alkenes, wherein a CF2H radical was generated from CF2HCOOH using (diacetoxyiodo)benzene (PIDA) and light [21]. This CF2H radical then added to the double bond to form a new alkyl radical, which underwent hydrogen atom

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

• cyclization to efficiently construct the pentacyclic intermediate 7, as demonstrated in our previous study [15]. Following the pioneering total synthesis of saframycin A (1) by Fukuyama and co-workers taking advantage of the compatibility of phenolic hydroxy groups with PS-type cyclization [22], other groups

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

• such, it is becoming increasingly essential for synthetic methods to align with a net-zero carbon future [2][3]. Therefore, advancing C1 chemistry remains a crucial endeavor for our group [4]. In synthetic organic chemistry, C1 compounds are usually installed using CO, CO2, HCO2H, CH3OH and CH4, which

• 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

• advancements in the synthetic transformations of dioxazolones, with particular examples of copper salts. Keywords: amidation; copper salts; dioxazolones; electrophilic nitrogen; N-acyl nitrene; Introduction Dioxazolones, first synthesized and reported by Beck and co-workers [1], have been employed as

• amidation Recently, Cao and co-workers reported the copper-catalyzed synthesis of 1,2,4-triazole derivatives via an N-acyl nitrene intermediate [76]. As illustrated in Scheme 3, dioxazolones 4 and N-iminoquinolinium ylides 5 served as reactive substrates, leading to the formation of various polycyclic 1,2,4

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

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

• asymmetric C(sp3)–H alkynylation of tertiary cyclic amines by merging Cu(II)/TEMPO catalysis with electrochemistry to yield chiral C1-alkynylated tetrahydroisoquinolines (THIQs) (Figure 5) [50]. As a co-catalytic redox mediator, TEMPO plays an essential role in the formation of iminium intermediate 15 and in

• 2022, Xu and co-workers established a site- and enantioselective cyanation of benzylic C(sp³)–H bonds using an electro-photochemical strategy (Figure 7) [55]. The reaction conditions show a broad substrate tolerance, and the late-stage functionalization of complex molecules derived from natural

• co-workers reported Cu-catalyzed asymmetric electrochemical regiodivergent cross-dehydrogenative coupling of Schiff bases and hydroquinones (Figure 9) [58]. In this approach, a chiral copper complex was used as a Lewis acid catalyst, yielding various synthetic routes for synthesizing chiral amino

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• JMS-T100GCV or a JEOL JMS-T200GC spectrometer. All the reactions were conducted under argon or nitrogen. Materials: Column chromatography was conducted on silica gel (Silica Gel 60 N, Kanto Chemical Co., Inc.). Toluene and N,N-dimethylformamide (DMF) were purified by a solvent-purification system