Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• further the applicability of the present synthetic method. Due to the excellent solvating power of CyreneTM, the “one-pot” synthesis of 1,2,3-triazoles could be proposed to eliminate the preparation and isolation steps of azide components. This could open an even greener and facile protocol for CuAAC

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• ]-cycloaddition of respective thiocarbonyl dipolarophiles (preferably non-enolizable thioketones) with diazomethane, was demonstrated as a favorable method for their generation [5][6]. In the past three decades, 1,3-dipoles 1 have extensively been studied as useful building blocks for the preparation of various

• (for synthesis of 4b,c, and 4e, see ref. [15]). The solution of diazomethane (CH2N2) in pentane was prepared without distillation and determination of the concentration following a procedure described in an earlier publication [28]. Preparation of 2c as a new precursor of thiocarbonyl S-methanide 1c

• . Witczak (Wilkes University) for stimulating discussions in the course of preparation of the manuscript. Funding Financial support by the University of Łódź within the IDUB grant (2023-2024) is acknowledged (G.M.). The authors (A. O. and M. D.-B.) thank the Polish Ministry of Science and Higher Education

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• experimental conditions. The choice of molecules that can be studied under ultra-high vacuum (UHV) is limited due to the requirement of their thermal stability and UHV compatible sublimation temperature. Therefore, the solution-based preparation method and solid-state measurements at ambient conditions hold

• accommodate ≈200 Tbits in a 1 cm2 area. Experimental Preparation of adlayer The FNAAP molecule is synthesized as per our previous report [29]. Ultra-thin films were prepared by drop casting from ethanolic solutions of molecules (concentration between 10−5 to 10−6 M) on freshly cleaved highly oriented

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• diterpenoids, including alterbrassicicene E and brassicicenes A and R in 4 or 5 chemical steps from brassicicene I. This strategy lays the foundation for the preparation of fusicoccane diterpenoids and their analogues for biological studies. Keywords: cotylenol; fusicoccane diterpenoids; heterologous

• chemical steps. This work lays the foundation for the preparation of fusicoccane natural products and exploration of their biological activities. Selected fusicoccane diterpenoids and overview of this study. (a) Representative members of the fusicoccane diterpenoid family. (b) This work: heterologous

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• bioactive compounds. According to the DrugBank there are more than 250 approved drugs classified as amides [2]. Just recently, between February 2021 and June 2022, sixteen anticancer drugs containing an amide bond have been approved by the U.S. FDA [3]. Consequently, the preparation of amides has garnered

• low tolerance to sensitive functional groups. Due to these reasons, alternative routes toward the preparation of amides are still in great demand in modern synthetic chemistry [5]. The arylation of isonitriles was introduced nearly a decade ago as an alternative synthetic pathway for the preparation

• . Control experiments, Figure S20). Conclusion In conclusion, a novel synthetic methodology for the preparation of benzamides from isonitriles and diaryliodonium salts has been proposed utilizing visible-light photoredox ruthenium-based catalysis. Both symmetrical and unsymmetrical diaryliodonium salts were

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• by Son and co-workers illustrates recent advancements in the use of dioxazolones in synthetic transformations with copper salts [4]. The authors remark that these catalytic systems, which employ dioxazolones as electrophilic amide sources, were applied for the preparation of diverse amidated products

• , who focus on the preparation of phenethylamines and phenylisopropylamines via reduction of substituted β-nitrostyrenes using a system of sodium borohydride and copper(II) chloride [9]. The transformations are performed in one pot and proceed under mild conditions. The β-nitrostyrene products could be

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• anti-inflammatory activity [8]. Moreover, they can be applied in disorders of the central nervous system, such as insomnia and Alzheimer’s disease [9][10]. The preparation of 2-aminobenzoxazoles classically proceeds via cyclocondensation reactions from pre-functionalised precursors, or via the C2

• efficiency. In the context of the C2 amination of azoles, to the best of our knowledge, only a few studies [48][50] have explored this approach, suggesting significant opportunities for further development and improvement. Building on our previous experience in the preparation and characterisation of

• in the preparation (theoretical loading). This suggests that optimum catalyst distribution and activity is achieved with 5 wt % supported CuCl. The two catalysts were also characterised by FTIR and DR UV–vis spectroscopy, to obtain information about the grafted aminopropyl ligand and inserted copper

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven B-3001, Belgium 10.3762/bjoc.21.104 Abstract A one-step method has been developed for the preparation of 2,3-dihydro-2-sulfonyl-3,4,5-substituted 1,2-thiazoles by the reaction of acryl thioamides and

• was synthesized. Experimental Thioamides 1a,f,g,l,r [19], 1b,c,d,e,j,u,x [20] and iodonium salts 2a [21] and 2f [22] were synthesized according to the previously described methods. The structures of all thioamides used in this study are provided in Supporting Information File 1. Preparation of

• precipitate was filtered off and washed with cold ethanol and diethyl ether. Preparation of 2-sulfonyl-2,3-dihydro-1,2-thiazoles 3 (general procedure). Method A. The corresponding thioamide 1 (1.0 equiv) and DCM (1 mL) was added to an oven-dried standard microwave vial with a volume of 10 mL. The resulting

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• ][33][34][35], especially in the realm of high pressure chemistry [36][37], in the present work we demonstrate a variety of new, catalyst- and additional solvent-free applications of HHP to develop green synthesis methods. Here, we describe several cyclization reactions for the preparation of a variety

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

• is to provide a comprehensive review of oxetanes in terms of their preparation and synthetic utility. Because multiple reviews of similar formats covering literature up to late 2015 have already been published [12][32][33][34], we will discuss primarily the most recent advancements since the year

• intramolecular E2 elimination. Finally, the importance and power of the intramolecular Williamson etherification has also been demonstrated by the kilogram-scale synthesis of oxetane intermediate 41, which is a key intermediate in the preparation of the previously mentioned IDO1 inhibitor 2 (Scheme 9) [16

• a preparation of oxetanes via silicon-directed electrophilic cyclisation of homoallylic alcohols 49 (Scheme 12) [46]. The reaction was promoted by a bromonium cation and moderate to high yields of oxetanes 50 were obtained. The authors claim the reaction was diastereospecific for disubstituted

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• R1 residue on the furan ring was found to have the most significant impact on the IMDA reaction. A bromine atom at the 3- or the 4-position resulted in products 8a–i in 66–86% yields, while a bromine atom or a methyl group at the 5-position inhibited the IMDA reaction in the preparation of 8j and 8k

• thiophene to reduce the diene's reactivity or altering the electrophilicity of the dienophile. Based on the computational analysis of the transition states, reaction mechanisms for the IMDA and the dehydration re-aromatization process are proposed in Scheme 5. In the IMDA reaction for the preparation of

• group on the imidazopyridine moiety have direct electronic impact on the IMDA reaction. This integrated reaction process provided a new avenue for the preparation of heterocyclic scaffolds with potential biological activity. Experimental General procedure for the synthesis of intermediates 4 and 6 The

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

• ) attached to the allyl precursor 114. Iteration of this process required ozonolysis of 113, followed by its conversion to an organometallic intermediate 116, which was then reacted with allyl 114 to yield another deoxypropionate product, 117. The synthesis began with the preparation of the precursor chiral

• undesired oxidation to the corresponding phosphane oxide. The work continued with the preparation of the chiral organometallic reagent 124. Starting from known bromide 122, which was readily accessible from Roche ester (R)-121 [52] or 1,3-diol 123 [53][54] through literature procedures, the Grignard reagent

• applications in medicinal chemistry. Chemical structure of borrelidin (1). Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41]. Preparation of monoacetates 37 and ent-38 by Uguen et al. [41]. Preparation of sulfones 27 and ent-27 by Uguen et al. [41]. Attempts to couple

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• Cinnamic acid derivatives represent a significant class of biologically active compounds exhibiting a broad spectrum of activities, such as antifungal, antidengue, antimetastatic, antimicrobial, antibacterial, and anticancer properties. Their preparation has attracted considerable attention due to their

• reaction (143) to activate the isothiocyanate as the coupling partner (Scheme 44) [83]. On the other hand, nucleophile activation could also be achieved via a catalytic oxidation reaction. For instance, Ablajan and co-workers (2024) reported the preparation of phenyl cinnamate (24) starting from the acid

• with nucleophilic cinnamonitrile 149 to give benzocyclooctene 150 via iodonium intermediate 151 (Scheme 46) [86]. 2.2 Oxidative acylations Cinnamic ester or amide preparation could also be achieved by oxidizing cinnamyl alcohol, aldehyde, imine, and ketone as an alternative to the traditional O/N

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• carbon precursors, including citric acid, glucose, and two kinds of biowaste, namely bass scales and blackberry residues arising from the production of preserves and jams and furnished by Rigoni di Asiago s.r.l. The strategy employed for the preparation of CDs were pyrolysis and hydrothermal treatment

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• further conversion of (S)-13a into the malononitrile derivative (S)-16 without loss of optical purity. Compound 1 and 2. Chiral ligands 3–7. Preparation and optical resolution of 7. Pd-catalyzed asymmetric allylic amination of acetate 12 (Ar = Ph) or 15 (Ar = p-ClC6H4) with isatin derivatives 11 using (aR

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• their accessibility for pharmacological measurements. Results and Discussion In the present study, we aimed to develop a novel, scalable synthesis of brevicarine (2) and an alternative synthetic approach for the preparation of brevicolline (1), both based on the common key intermediate 3 [9]. The

• has been elaborated rendering the preparation of larger amounts of the target compound possible. NMR data of brevicarine base and dihydrochloride salt were fully assigned for a further confirmation of their structure. In the course of the unsuccessful attempts for a new synthesis of brevicolline, we

• nitrovinylindole 19. New synthesis variants for the preparation of brevicarine alkaloid (2) and its synthetic derivative N-methylbrevicarine (27). Preparation of carbamate 28 and subsequent reduction with LiAlH4. Experiments for the synthesis of racemic brevicolline ((±)-1), and formation of unexpected products

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• essential tertiary alcohol at C1. The β-hydroxylactone moiety (D ring) in 11 could be introduced through an intramolecular aldol condensation [35] of acetate 12. Ultimately, the preparation of 12 could be traced back to aldehyde 14 through 1,2-Grignard addition with an organomagnesium reagent [36] prepared

• from α-iodoenone 13. Our synthesis began with the preparation of α-iodoenone 13 (Scheme 2). The α-monomethylation of cyclohexenone 15 was efficiently carried out with LDA, HMPA, and MeI [37], producing enone 16 in 78% yield. Subsequently, a diastereoselective aldol reaction between 16 and 3-furaldehyde

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• electrosynthesis as a green, precise, and low-cost method to prepare phosphorous structures. Keywords: electrosynthesis; green synthesis; organophosphorus compounds; P–C bond formation; P–heteroatom bond formation; Introduction The electrochemical synthesis is a valuable and beneficial method for the preparation

• the gram-scale preparation of some samples. An electrochemical flow system was used in this method, in which carbon and platinum electrodes were used as the anode and cathode, respectively, at a constant current of 55 mA (Scheme 8). Due to the steric hindrance caused by the tert-butyl group, the

• )(OR)2. The final product was formed by a simple nucleophilic substitution of the phosphorus center (Scheme 20). The N–P bond formation is a critical process in organic synthesis due to the preparation of various materials with different biological and medicinal activities. In 2021 Wang et al. [65

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• potency as inhibitors of Man-specific bacterial adhesion investigated. Results and Discussion Synthesis For the preparation of the homobivalent glycocluster 6αMan3αMan 2, the known mannosyl thioacetate 7 [31] was prepared from the trichloroacetimidate 6 [32] and thioacetic acid in an α-selective reaction

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

• , including non-toxicity, bench-stability, structural diversity, straightforward preparation, and broad commercial availability. Significant contributions include Sawamura's work with alkyl–9-BBN [32][33][34][35][36][37] as a nucleophile. These developments have collectively transformed copper-catalyzed AAA

• (+)-lasiol was achieved through a highly selective SN2 substitution (SN2/SN2' = >99:1, dr = 98:2, 99% ee), while the preparation of (+)-13-norfaranal and (+)-faranal showcased the versatility of the methodology in constructing more complex terpene frameworks. These successful applications in natural product

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• mM concentration, respectively, in 5:1 MeCN/H2O (0.1 M Et4N–BF4). B) Anodic oxidation of pyrrolidine 6a. Plausible mechanism for formation of pyrrolidine 6a and hemiaminal 10a. Preparation of malonic acid monoester 9a. Electrolysis of acid 9d in deuterated solvents. Scope of the decarboxylative

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• ]. Semisynthesis of massarilactone D derivatives Preparation of compound 2 Massarilactone D (1, 15 mg, 0.062 mmol) was dissolved in CH2Cl2 (10 mL). Triethylamine (20 μL) and methacryloyl chloride (30 μL, 0.31 mmol) were added to the solution. After adding a catalytic amount of 4-dimethylaminopyridine, the reaction

• (C-4a), 83.7 (C-2), 82.3 (C-2'), 69.9 (C-3), 62.3 (C-4), 31.4 (C-3'), 26.0 (C-4'), 25.1 (Me-2'), 23.5 (C-11), 18.3 (Me-2''), 18.2 (Me-5'), 18.1 (C-10, Me-2'''); HRESIMS (m/z): [M + Na]+ calcd for C27H31O10NaCl+, 573.1498; found, 573.1495. Preparation of compounds 3 and 4 Massarilactone D (1, 15 mg

• '''), 129.3 (C-5', C-9'), 124.2 (C-8), 117.9 (C-2', C-2'', C-2'''), 100.9 (C-7), 99.3 (C-4a), 83.2 (C-2), 69.7 (C-3), 62.2 (C-4), 23.6 (C-11), 18.2 (C-10); HRESIMS (m/z): [M + H]+ calcd for C38H32O9+, 633.2119; found, 633.2077. Preparation of compound 5 Massarilactone D (1, 15 mg, 0.062 mmol) was dissolved in

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• unambiguously confirmed by X-ray diffraction. Keywords: allomaltol; enamines; 2H-furo[3,2-b]pyran-2-ones; pyrazol-3-ones; recyclization; Introduction Substituted furan-2(5H)-ones (butenolides) are widely used as precursors for the preparation of diverse types of heterocyclic compounds possessing various

• communication we investigated the interaction of substituted 2H-furo[3,2-b]pyran-2-ones 1 with nitrogen-containing nucleophiles (Scheme 1b, this work). As a result, the general approach to preparation of pyrazolones with a 3-hydroxy-4-pyranone unit was developed. It’s important to underline that both pyrazolone

• elaborated above for the preparation of enamines 4. Interaction of starting compound 1a with hydrazine was performed using acetic acid as a solvent at reflux for 8 h. As a result, the appropriate pyrazolone 10a, unsubstituted at both nitrogen atoms, was obtained with 73% yield (Scheme 5b). Based on 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

• excellent enantioselectivities (Figure 1c). Despite these successful examples, the construction of only one stereocenter has been reported to date. The Mannich reaction has great importance because of its utility in the preparation of useful chiral molecules such as amines [36], amino acids [37], and amino