Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• -arylidene derivatives (5-arylidene-2-thioxothiazolidin-4-one or 5-arylidenethiazolidine-2,4-dione), which have attracted the attention of medicinal chemists, and, consequently, several strategies have been created to synthesize these molecules [38]. The main methodology comes from the Knoevenagel

• condensation-type reaction using ethylenediamine (EDA) as catalyst in AcOH under microwave (μw) heating. This convenient methodology is broad in scope, provides the condensation products in high yields (up to 99%), with a reasonable catalyst loading (10 mol %) in only 30 minutes. This approach also enabled the

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• scalable methodology overcomes limitations of prior syntheses, enabling biological evaluation. Keywords: Fmoc-solid-phase peptide synthesis (Fmoc-SPPS); head-to-tail cyclization; plant cyclopeptides; Vaccaria segetalis; Introduction Cyclopeptides have garnered significant research interest owing to their

• purity of the synthetic segetalins. CD spectroscopy provided insights into their secondary structural preferences. This robust and scalable methodology overcomes significant limitations of previous synthetic approaches, providing ample quantities of these bioactive cyclopeptides for detailed biological

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• organic chemistry, and particularly in the late-stage functionalization of bioactive compounds, drugs, and natural products. This review highlights recent advances in NHC–organophotoredox dual catalysis, focusing on methodology development, mechanistic insights, and reaction scope for synthesizing

• mild conditions, using sustainable methods with low-cost materials, and using non-toxic reagents. Its proven potential includes medicinal chemistry, pharmaceuticals, materials science, and the late-stage functionalization of complex bioactive molecules. Recent synthetic advances in methodology

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• stereocenters characteristic of the target molecule, the authors strategically implemented this methodology. This approach efficiently established two carbon–carbon and four carbon–oxygen bonds while introducing four contiguous stereocenters, successfully assembling the highly functionalized AB ring system

• this natural product family while stimulating further innovation in synthetic methodology. Evidently, the synthesis of Ryania diterpenoids remains one of the most formidable challenges in contemporary synthetic chemistry. The development of more efficient and broadly applicable synthetic strategies

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• constructing the ABCE tetracyclic cores of Aspidosperma alkaloids from tryptamine-substituted cyclobutenones. Importantly, this methodology has already been successfully applied in the total syntheses of (±)-aspidospermidine and (±)-limaspermidine using 10a and 10h as substrates, respectively [26]. The

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• handling, storage, and transfer of this toxic gas becomes a safety issue. To enable the facile and safe use of trifluoroacetonitrile, and other partially fluorinated acetonitriles, we set out to develop a methodology, which enabled facile use of these gases based on Parker’s method [13], i.e., generating

• conclusion, we have developed a simple and safe methodology for the on-demand ex situ generation of stoichiometric amounts of gaseous haloacetonitriles in a closed system at room temperature. The methodology is safe, robust, and operationally simple on a laboratory scale. The method was exemplified by the

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• development of a new methodology for the synthesis of galactofuranoside building blocks, we encountered an unexpected predominance of the furanoside form in the equilibrium mixture of benzoylated β-galactosides. Since the furanoside form is typically less stable and is usually present only in minor amounts

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• ]. When a para-fluorine substituent is present on the naphthalene ring of the substrate, the reaction proceeds with a yield of up to 90% and an enantioselectivity reaching 92% ee. The methodology demonstrates a broad substrate scope, accommodating various polycyclic naphthalene isoquinolines as well as

• or cationic species. In 2019, Qin and co-workers reported a methodology enabling the difunctionalization of alkynes through selenosulfonylation of a VQM intermediate under mild reaction conditions [20]. This racemic transformation proceeds without the need for any catalyst or additive, and the

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• exhibit a wide range of biological activities [26][28][31][32][33][34][35]. The validity of the atom-efficient methodology under discussion has been demonstrated in experimental research; its efficacy in facilitating the rapid formation of multifunctional complex molecules being in contradistinction to

• the time- and labor-intensive nature of traditional multistep synthesis strategies. For instance, this methodology has been demonstrated to be highly advantageous in the synthesis of numerous pharmaceutical compounds, biological probes, insecticides, alkaloids, and other intricate natural compounds

• a more appropriate and eco-friendly solvent. Furthermore, a multitude of alternative vegetable oils could also be considered as green reaction media for such reactions. The pyrrolo-isoxazolidines targeted for synthesis in this Green Chemistry methodology were obtained as cis/trans diastereoisomer

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• for constructing spiro[indoline-3,2'-pyrrolidine] derivatives via a sequence involving the reaction of 2-arylindoles with α,β-unsaturated ketones, followed by Fe(II)-catalyzed spirocyclization of the corresponding easily accessible oxime acetates. The methodology exhibits broad substrate scope, with

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• late-stage lactonization as key steps [26] (Scheme 1). Subsequently, they achieved the asymmetric synthesis of vibralactone (6) based on the asymmetric Birch reduction–alkylation methodology developed by the Schultz group [27][28]. In 2016, Brown and co-workers described an efficient synthetic route

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• as reductive elimination [62]. G. Liu and Stahl disclosed an elegant methodology to functionalize benzylic C–H bonds via copper catalysis [30]. Under the catalytic conditions, alkylarenes were converted to benzylic nitriles in good yields and excellent enantioselectivities. In the proposed mechanism

• phosphoric acid catalytic system [31]. Aminoalkenes react with Togni’s reagent in the presence of a catalytic amount of CuCl and a chiral phosphoric acid to yield pyrrolidines. Using this methodology, chiral α-quaternary substituted pyrrolidines were synthesized in good yields and excellent

• enantioselectivities. A radical chaperone methodology is based on a multicatalytic system in which a chiral Cu(I) catalyst, Brønsted acid (camphoric acid) and Ir photocatalyst work synergistically. An asymmetric synthetic method based on radical C–H functionalization was reported by Nagib and co-workers for the

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• metal-free methodology delivered synthetically versatile iodinated homoallylic alcohols bearing piperidine motifs and pyrrolidine-fused cyclopropanes. Importantly, the reaction was carried out with high operational simplicity and environmental compatibility under mild reaction conditions. In 2024, Chan

• intermediate 76 to drive hydrolysis. This methodology tolerates structurally diverse 1,7-enyne esters and generates defined cis-1,2,3,6-tetrahydropyridine scaffolds, which serve as synthetic intermediates for complex natural products and pharmacologically relevant heterocyclic frameworks. In 2016, Jiang group

• , affording the eight-membered benzo[b]azocin-2-one product 165. This methodology was distinguished by operational simplicity, high efficiency, and scalable synthesis. Moreover, temperature modulation achieved rapid access to cyclic compounds with distinct ring sizes. In 2022, biphenyl-embedded 1,3,5-trien-7

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• -catalyzed side-reaction. As shown above, the steric hindrance plays a significant role in driving the reaction. For this reason, we have applied our novel Pd methodology to synthesize a series of tetra-, tri-, and di-ortho-substituted azobenzenes (Scheme 3). Notably, this method demonstrates remarkable

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

• that this report provided a switchable and green synthetic methodology for skeletally diverse indoles. Divergent electrochemical cyclization of 2-ethynylanilines was developed to synthesize indoles and iodoindoles (Scheme 4) [188]. Treatment of 2-ethynylanilines 10 with KI in DMSO/H2O in an undivided

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

• . We hope this review can stimulate the methodology development and application of this strategy toward further improving the synthetic efficiency of natural product synthesis. Review Total synthesis of terpenoid and alkaloid natural products through the desymmetric enantioselective reduction of five

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

• enantiomeric natural products have been discovered [21][22][23][24][25][26][27][28][29][30][31][32], and divergent synthetic methodology has attracted attention in recent years [33][34][35][36][37][38], diastereodivergent and enantiodivergent total synthesis remain rare [39][40][41][42][43][44][45][46][47][48

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• linker provides entry to 1,2,3,6-tetrahydropyridines. Additionally, in the absence of internal nucleophiles, this methodology yields aryl-substituted 1,3-dienes. This work introduces a palladium-free, single-step alternative to multistep heterocycle construction from propargylsilanes and highlights the

• have been induced by addition of external halogen or selenium electrophiles and Brønsted acids. This encouraged us to develop a methodology involving a copper-catalyzed terminal alkyne arylation of propargylsilanes by diaryl-λ3-iodanes, followed by 1,2-silyl shift and terminated by nucleophile addition

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

• asymmetric synthesis of them, driving the advancement of asymmetric methodologies [5][6][7][8][9]. Enantioselective desymmetrization of symmetric substrates has emerged as a pivotal methodology for the construction of chiral centers over the past few decades [10][11][12][13]. A series of reaction types have

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

• diimines of aromatic aldehydes with trans-1,2-diaminocyclohexane for the synthesis of enantiopure tetrasubstituted piperazines has been investigated by an electrochemical approach. The methodology was successfully developed under both batch and continuous flow conditions, and afforded enantiomerically pure

• diimines (Scheme 4). This methodology has been successfully applied to the synthesis of enantiopure tetrasubstituted piperazines, featuring both electron-withdrawing and electron-donating groups on the aromatic rings. Results and Discussion The stereoselective electroreductive intramolecular coupling of

• methodology, the trans-1,2-diaminocyclohexane was replaced with (S)-1,1′-binaphthyl-2,2′-diamine. Under the optimized conditions, the corresponding cyclic product 2k was obtained in 34% yield, consistent with previous observations reporting reduced efficiency as the ring size increases [44]. To confirm the

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

• stereoselectivity for the more sterically demanding aza[5]helicene 3c and aza[7]helicenes 3d–f. Furthermore, the authors expanded this methodology to a double Fischer indolization reaction between hydrazine 1i and ketone 2i, which yielded diaza[8]helicene 4 with moderate yield and high enantioselectivity after

• aromatization process, in 2023 our group reported the asymmetric synthesis of various azahelicenes 8 from polycyclic arylamines 5, dienamides 6 and aldehydes 7 (Scheme 2) [13]. This methodology demonstrates a broad substrate scope, enabling the efficient asymmetric synthesis of diverse aza[5]helicenes 8a–d and

• reaction produced the imine 16a which, upon treatment with Pd(PPh3)2Cl2 and KHMDS, led to furan ring formation and the generation of hetero[7]helicene 17a while maintaining the stereochemical configuration. Through this methodology, a range of elongated [7]- and [8]heterohelicenes 17b–d incorporating both

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

• this methodology. As summarized in Scheme 2, we initially investigated the scope and effect of arylamine functionalities on this transformation. Under optimized reaction conditions, arylamines bearing either electron-rich or electron-deficient substituents at the para-position demonstrated good

• , resulting in the formation of both 3r and 3r′, which were obtained in 86% combined yield. Gram-scale studies were conducted to further demonstrate the synthetic potential and practical utility of the developed methodology. The biologically significant compounds 6-(tert-butyl)-2,4-diphenylquinoline (3d) and

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

• dispersion corrections to improve the modeling of nonbonding interactions [23]. The same computational protocol was applied to cyclopropane, methane, and methyl fluoride, used as reference molecules in the isodesmic reactions. This methodology has proven reliable for predicting the energetics and properties

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• . Analysis methods: A statistical analysis (Figure 4d) indicates that over 80% of analyses for continuous-flow nitration processes employ the one-factor-at-a-time (OFAT) methodology [57]. This approach inherently relies on scientific intuition, where experimental campaigns are conducted through iterative

• systems. A well-established framework has emerged for modeling nitration kinetics in homogeneous systems, with the following generalized methodology currently adopted across mechanistic studies. Reaction kinetics in homogeneous systems: The model reaction for the homogeneous nitration reaction by nitric

• nitration scale-up processes. HAZOP (hazard and operability study) also serves as a pivotal safety assessment methodology in continuous-flow nitration process development, leveraging its systematic framework for risk identification and process safety optimization. For instance, the nitration of toluene is

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• :1 dr, 99% ee). Subsequently, we expanded this methodology to prochiral N-quinazolinone maleimides 59, achieving the simultaneous generation of N–N axial and central chirality within a single step (Scheme 9b) [56]. Of particular note, an interesting ligand-induced diastereodivergent profile was