Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• methods for the synthesis of tetrazoles [25][26][27][28], the Ugi–azide reaction is a good approach for constructing 1,5-disubstituted-tetrazoles (1,5-DS-T) [29][30][31]. This scaffold can be subsequently linked to 1,2,3-triazole [32], 4H-chromen-4-one [33], pyrrolo[3,4-b]indolizine [34], and other

• heterocyclic scaffolds to obtain biologically interesting compounds (Scheme 1) [35][36][37][38][39][40][41]. The development of methods for the synthesis of triazole, tetrazole, piperazinone, and 1,4-benzodiazepine motifs are attractive from both synthetic and medicinal chemistry considerations [42][43][44][45

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• radical cation G [232]. The following intramolecular cyclization/anode oxidation produced intermediate I that was then deprotonated to yield the target 33a. Compared to the previous reported methods [233][234][235][236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251][252][253

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• , and illustrating their high-value conversion methods towards fine chemicals. Review C2 biobased carbonyl platforms Glycolaldehyde Developing accesses from biomass to structures such as glycolic acid (GA) and glycolaldehyde (GCA) with high atomic economy is challenging. Hu et al. reported a new route

• evolves towards cyclic acetals (Scheme 4) [32]. Exploring methods for the conversion of glycolaldehyde (GCA) to 3-(indol-3-yl)-2,3-dihydrofurans in organic solvents, Gu et al. reported a three-component reaction combining GCA, ethyl acetoacetate as 1,3-dicarbonyl component and indole. Using glycolaldehyde

• ]. Matsumura et al. [108] reported the biocatalytic conversion of butane-1,2,4-triol into 1,4-dihydroxybutan-2-one. This work dealt with the conversion of sec-hydroxy groups to carbonyl derivatives by methanol yeast, Candida boidinii KK912, a cheaper and simpler process compared to other methods. The product

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• , the development of novel methods and strategies to achieve efficient asymmetric total synthesis of complex terpenoid and alkaloid natural products has drawn considerable attention from synthetic chemists. Over the past decades, the development of desymmetric enantioselective reduction strategy of

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• optimization of promising lead structures has therefore inspired the development of powerful synthetic strategies. A glance at Web of Science reveals that one-pot methods and multicomponent reactions (MCRs) [1] have attracted steadily increasing attention within the scientific community over the past 25 years

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• alkaloids and antipodes. Enantioselective synthesis of the proposed structure of aspera chaetominine A. Enantioselective syntheses of both the proposed and revised structures of aspera chaetominine B. Supporting Information Supporting Information File 4: General methods and materials, experimental

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• a series of 6-aminomethyl-substituted indoloquinazoline derivatives 14а–d (Scheme 5). The structures of all compounds were analyzed and confirmed by NMR and HRMS methods. Samples of all indolo[1,2-c]quinazoline derivatives with good analytical purity (HPLC, ≥95%) were further subjected to biological

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• catalytic asymmetric methods [26], we intended to probe this biomimetic oxidative cyclization transformation [27][28]. In 2013, we first used monocerin as a model target molecule to initiate our study (Scheme 3a). Starting from benzaldehyde 11 with an isopropyl group on the hydroxy group in 4-position

• subsp. brachystachys, and discovered a series of complex natural products named sargalmides A–E [43] (Scheme 7a). To clearly elucidate the complex structures, Yue and co-workers used multiple methods including extensive spectroscopic analysis (NMR, IR and MS), X-ray crystallography, quantum-chemical

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• transition behavior, achieving high gravimetric energy densities (300–400 J/g) with long-term storage stability (Figure 6d). Grossman and Durgun proposed methods for incorporating azobenzenes into macrocyclic structures [82]. Their computational models indicated that the molecular rings connecting the

• forward, improving the energy storage density of azobenzene-based solar thermal fuels remains an important research direction. However, significant opportunities exist for developing azobenzene derivatives that absorb visible light to NIR. In terms of charging and discharging methods, solvent-free systems

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• -1,2,4-triazoles, is important because the formation of different chemotypes of final heterocyclic compounds are possible depending on the structure of the reagents, the solvents and the catalysts, and type of activation methods [7][8][9]. MCRs of aminotriazoles, methylene-active compounds, and

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• with the addition of 0.1% formic acid. The use of other eluents such as acetonitrile and different ratios of hexane/ethyl acetate, dichloromethane/methanol as well as the application of methods for the isolation of triphenylphosphine oxide by complexation with calcium and magnesium salts [54][55] or

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• products were the same those obtained by thermolysis, nitrogen and bicyclo[2.1.0]pentane with quantum yield approaching unity [64]. Engel and co-workers explored further the reaction using transient spectroscopic methods and discovered that the rate of N2 formation is significantly slower than that the S1

• Table 1. The S0 → S1 vertical excitation energy, calculated using XMS-CASPT2(8,9)/ANO-S-VDZP, ranges from 3.94 to 3.97 eV and has the electronic transition from nNN(σCN) to π*, with an oscillator strength of 0.013 for all molecules. The S0 → S2 excitation involves an nNN → π* transition with all methods

• couplings at each 0.5 fs timestep. Our results indicate that the retained stereochemistry of housane is generated in the ground state via thermal conversion from inverted housane/diradical. Computational Details Single reference methods We used density functional theory (DFT) to optimize the ground-state

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• parameterization of asymmetric reactions remains unavailable, and the remoteness of stereocontrol for reactions that establish non-central chirality is judged based on empirical chemical intuition. While developing catalytic methods to establish remote stereogenic elements, we became increasingly interested in

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total

• methods for sensitive detection of endogenous PGD2 production and its stereoisomers are clinically important [5]. However, PGD2 is rapidly metabolized with a short half-life, making the identification and quantification of its downstream metabolites a promising and reliable diagnostic tool. Tricyclic

• effective tool in clinical applications [6]. However, the scarcity of metabolite 4 has prevented it from being used more widely, and thus synthesis methods for 4 are required. Compound 4 contains a cyclopentanol scaffold with stereogenicity at C8, C9, C11, and C12 (Scheme 1A). In addition, 4 is

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• reactions, chemists have developed a series of catalysts composed of transition-metal cores and chiral ligands, which have been applied to various asymmetric reactions [50][51][52]. Compared to the enzymatic methods, the transition-metal-catalyzed approach may provide an advantage to access both enantiomers

• transition-metal-catalyzed acylations is a notable advantage compared to enzymatic methods. In the case of local desymmetrization, the enantioselectivity of the reaction depends predominantly on the inherent properties of the substrate. Although numerous examples of enantioselective desymmetrization

• reactions of prochiral 1,3-diols via metal-catalyzed and enzymatic methods have been reported, these transformations are mostly limited to the acylation of hydroxy groups. Other reaction types, such as sulfonylation, oxidation, and coupling, remain underdeveloped in this context, suggesting significant

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• isolated and structurally characterised (using, where appropriate, HMBC, COSY and nOe NMR methods; see Figure 3). In general, the yields of these products were rather low, which may stem from poor (co-)substrate solubility in some cases; and/or competitive O–H insertion into adventitious water. On the

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• interactions. The method provides insight into protein structures and functions using electrochemical methods that can also be applied to studies involving alkylating agents [25][26]. In this study, LSV was employed to investigate the interactions between human serum albumin (HSA) and the three prospective

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• conditions, the continuous process afforded higher productivities and space-time yields than the batch reactions due to a short residence time. This work provides a mild, efficient, and scalable alternative to traditional methods for the synthesis of tetrasubstituted enantiopure piperazines, with potential

• photochemical and electrochemical methods, have been explored. Over the past two decades a variety of light-promoted imino-pinacol coupling reactions have been developed, involving the use of catalytic transition-metal complexes [35][36], organic dyes [37][38][39], and polyaromatic compounds [40][41] as

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• is in part due to limitations in the quantities obtained in the extraction processes. Other selected examples shown in Figure 1 all contain the same spirocyclic oxindole with a bridged azabicyclo[3.2.1]octane moiety. Several methods to access spirocyclic oxindole alkaloids have been reported [7][8][9

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• furan and pyridine moieties were successfully synthesized with high enantioselectivity. These compounds would be challenging to access using alternative asymmetric methods. In 2025, our group disclosed a highly efficient catalytic enantioselective double annulation approach for the asymmetric synthesis

• good yield and excellent enantioselectivity (Scheme 5). Notably, two distinct oxidative aromatization methods have been developed to yield diverse heterohelicene products. For instance, using DDQ as an oxidant selectively delivered hetero[7]helicenes 19 with monoamido substitution at the peri-positions

• , planarly chiral and inherently chiral molecules across diverse research fields, has spurred considerable research focus toward the catalytic asymmetric synthesis of these unique chiral molecules. While methods for the asymmetric synthesis of these chiral molecules remain relatively underexplored compared

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• of the metastable isomer [5][6][7], thus they are also important factors to consider when choosing the solvent and the concentration of the solution. The half-life can be extrapolated by monitoring the photoswitch in the metastable form over time by various spectroscopic methods (UV–vis, NMR) in the

• number of irradiated photons ntot: Quantum yields vary in the range 0 ≤ Φ ≤ 1 and can be calculated by spectroscopic methods [8]. The calculation, however, is not trivial because irradiation can trigger various photochemical events. For instance, if the spectra of the two isomers strongly overlap, both

• properties and tuneability while also outlining the most common synthetic methods for these compounds. Additionally, each chapter presents exemplary applications of the illustrated photoswitch classes, highlighting their practical relevance while inspiring the reader with new ideas in this field. For a more

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• [18]. Due to its wide range of applications, several methods for synthesizing substituted quinoline derivatives have been developed in recent decades, based on mechanisms such as Conrad–Limpach–Knorr [19], Friedländer [20], Doebner−Miller [21], Pfitzinger [22], Skraup [23], Povarov [24], and Combes

• [25]. However, these methods often require multiple synthetic steps and demanding conditions such as elevated temperatures, strong acidic or basic environments, and the use of expensive metal catalysts, which limit their broader applicability. To overcome these limitations, numerous catalytic

• light of climate change and the ongoing energy crisis, there is an urgent need to reform energy and chemical production by prioritizing environmentally sustainable methods that are both practical and broadly implementable. Styrenes are industrially important bulk chemicals [39], with an estimated global

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• -membered heterocyclic ring are of particular interest, since they exhibit a wide range of pharmacological activity (Scheme 1) [6][7][8][9][10][11]. The most straightforward and powerful methods of such substance’s syntheses are based on cycloaddition reactions [12][13][14][15]. Previously, we and other

• ) and found that only these two abovementioned approaches are capable to perform desired cycloaddition (Supporting Information File 1, part 2). For various azolones 1–5e, these two methods demonstrated different efficiency – Table 1. Derivative 6e was formed from azolone 1e in approximately equal yield

• provided by both methods (with cesium fluoride being preferred), while for rhodanine 3e this method was able to produce almost quantitative yield of cycloadduct 8e. In contrast, for hydantoin 2e and imidazolone 4e the use of TBAF was preferable. It is interesting to note that in all cases, we obtained only

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• –guest complexation realizes a reversible ON-OFF-ON type pseudo-monomeric ligand-gated ion transport switch [91]. The development of these pillararene-based materials has enriched the dynamic regulation methods of supramolecular structures and provided innovative approaches for prodrug design. 2 Stimulus

• employed as an external trigger for supramolecular systems. Azobenzene can regulate geometry, shape, and interfacial curvature under ultraviolet or visible light irradiation. It undergoes cis–trans isomerization, which can trigger alterations in bioactivity or assembly configurations. Methods for creating

• various stimuli used to control responsive assemblies, enzymatic methods offer several benefits, including biocompatibility, high efficiency, specificity, and mild reaction conditions. Liu and colleagues reported an enzyme-responsive supramolecular ternary polymer (DiCh@a-CD-bisSC4A) (Figure 12) [95]. The

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• molecules (QTAIM) analyses were carried out with the AIMAll program [27]. Structures of fluorinated cyclopropanes evaluated in this study through quantum chemical methods. (a) Electrostatic potential map of 1.2.3-c.c., highlighting the negative region (top side) and positive region (bottom side). (b) Top