Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• ]. Other methods necessitate the umpolung modification and the reestablishment of the original group in separate reaction steps [3][4]. Additionally, there are approaches that represent only conceptual umpolung, utilizing synthetic equivalents that are not directly related to the target functional group

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• , needles, and bark of certain trees. In particular, the bark of larch trees contains 0.1–2 wt % maltol (2) and economic isolation methods using for example aqueous tannin liquors with extraction efficiencies of >90% have been developed [22][23][24]. Owing to the natural availability of maltol (2

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• , structures, and redox properties, effective synthetic strategies for the construction of N–N and N–O systems remain markedly underdeveloped. Unlike traditional methods for constructing C–C and C–Het bonds, the number of methods for selective N–N [1][5][19][20][21][22][23][24][25][26][27][28][29] and N–O [30

• and N–O bond formation. However, it also represents a highly efficient and valuable strategy due to the synthetic availability of starting materials. Therefore, the development of new methods for direct selective N–N and N–O coupling remains an important goal in synthetic chemistry. To date

• electrochemical cell distinguishes electroorganic synthesis from traditional organic chemistry methods. Particular attention is paid to the generation of radical intermediates via the oxidation or reduction of radical precursors [40][41][42][43][44][45][46][47][48][49]. In this regard, the anodic oxidation of

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• members of prenylated indole alkaloids exhibiting α-glucosidase activity is described. Asperdinones B, C, D, and E are characterized by the presence of a (3R)-3-indolylmethylbenzodiazepine-2,5-dione unit at C-3 of C4–C7 prenylated indoles. Methods of direct and indirect prenylation of indole and

• tryptophan were explored. Different approaches were adopted for the functionalization of C4–C7 prenylindoles at C-3 using Negishi cross-coupling methods. The asperdinones are among the rare tryptophan-derived indole alkaloids which appear to have undergone epimerization due to genetic alteration of specific

• bond formation and functional group compatibility presented unforeseen challenges. Methods for the chemical synthesis of prenyltryptophans (approach A, A–C) are scarce [25][26]. Adopting a bio-inspired approach, Ishikawa et al. treated tryptophan ethyl ester with prenyl alcohol in the presence of 2

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• -component cyclization; Introduction The modern strategy of organic synthesis is aimed at conforming to the "green chemistry" principles based on PASE (pot, atom, step, economic) methods. These principles serve as the foundation for multicomponent processes that allow various structurally complex molecules

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• from chemists as it is one of the most expedient and direct methods for the formation of a new C–S bond [9][10][11]. Thiocyanates represent a valuable class of molecules serving as versatile intermediates [12][13][14][15] in the synthesis of a broad range of organosulfur compounds, including thiols

• thiocyanate group is introduced into a molecule bearing a nucleophile in a suitable position, cyclization can readily occur. In recent years, several methods for the hydrothiocyanation of alkynes bearing functional groups, primarily alkynoates, have been developed. Thus, thiocyano enoates were synthesized via

• available starting materials were used without further purification. CF3/n-C3F7-substituted iminopropargyl alcohols 1 were prepared according to published methods [31][32]. The structures of synthesized products have been proven by 1H, 13C and 2D (1Н,13С HMBC) NMR, 19F NMR techniques, as well as IR spectra

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• cores through modular and strategic bond connections, but they also give a reflection on the advancement of modern synthetic methods and retrosynthetic logic. This review will cover recent syntheses, highlighting the convergence of modern strategic disconnections, stereocontrol, and late-stage

• embedded in A–E rings, thus, adding to their complexity in total synthesis efforts [9]. This review will cover synthetic approaches from the last decades, showcasing the evolution of Veratrum alkaloids synthesis and by that, providing an impression of the evolution of synthetic methods in general. For a

• effect of today’s methods in comparing to this strategy, while the Masamune group had to choose from much more limited methodology, resulting in tedious protecting group strategies, several reprotections, and redox manipulations [14]. Comparison of strategies for the jervanine-type In total, cyclopamine

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• of compound 23a was proven by single-crystal X-ray diffraction (Figure 4). Starting from compound 7, using methods we have previously developed for the synthesis of related compounds [2][3], we have now prepared new pentacyclic ring systems 25–27 (Scheme 5). Demethylation of 7 followed by alkylation

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

• [52], acetic acid [53], or solvent-free processes [54]. Ionic liquids, such as [Bu4N][OH] [55], [bmim][OH] [56], and [Et3NH][HSO4] [57], and deep eutectic solvents (DES) [58] have been introduced to improve efficiency. Traditional methods for synthesizing these compounds, however, face several

• inconsistency made it challenging to rely on NMR as the primary method for confirming the structure of the expected products. To overcome this limitation, other analytical techniques, such as mass spectrometry and infrared (IR) spectroscopy, were employed. These methods successfully corroborated the formation

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

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• continued integration of this versatile photocatalytic platform with sustainable methods such as visible-light harvesting and the use of earth-abundant catalysts is expected to further enhance its impact across diverse research fields, including chemical biology, pharmaceuticals, agrochemicals, polymers

• cross-coupling between the C-centered and N-centered radicals. These methods are expected to open new avenues for visible-light- and NHC/4CzIPN-catalyzed carbon–heteroatom bond-forming processes (Scheme 1) [51]. In 2021, Studer et al. developed a novel method for the 1,3-difunctionalization of

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

• Zhi-Qi Cao Jin-Bao Qiao Yu-Ming Zhao Key Laboratory of Applied Surface and Colloid Chemistry of MOE & School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, 710119, China 10.3762/bjoc.21.198 Abstract Innovations in synthetic methods and strategic design serve as the

• primary driving forces behind the advancement of organic synthetic chemistry. With rapidly evolving organic synthesis technologies, a diverse array of novel methods and sophisticated strategies continues to emerge. These approaches not only complement and synergize with one another but also significantly

• focuses on reviewing the efficient application of ring-construction methods and synthetic strategies in the total synthesis of highly oxidized Ryania diterpenoid natural products, emphasizing the pivotal role of novel synthetic methods and strategic innovations. Keywords: natural products; Ryania

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• promising candidates for further investigations as a drug delivery system. The entrapment of different drugs combined with the intrinsic anticancer activity of the nanoassemblies could provide new agents for a combination multidrug anticancer treatment. Experimental Materials and methods: All chemicals were

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• Supporting Information Supporting Information File 4: Description of materials, experimental methods, synthetic procedures, analytical characterization and copies of NMR spectra for novel compounds. Funding Research reported in this publication was supported by the National Institute of General Medical

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• perform equally well using conventional heating methods. Aniline 10 and carboxylic acid 13 were combined under standard (HBTU) amide coupling conditions to afford benzyl ester 14 in 52% yield. Compound 14 was subsequently debenzylated via hydrogenolysis to afford the target Db2 monomer 15 in 77% yield

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• and functional materials (Scheme 1a) [62][63][64][65][66]. Traditional electrophilic aromatic substitution methods for the nitration of carbazole typically result in a mixture of 1-nitro-, 2-nitro-, and 3-nitro-substituted isomers (Scheme 1b) [67]. Therefore, developing a method for the regioselective

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

• formation of unique radical intermediates [9][10]. We previously demonstrated the Ir-catalyzed [2 + 2] cyclization/retro-Mannich reaction of a tryptamine-substituted cyclopentenone F, which led to the formation of indoline J (Figure 1b) [15]. Unlike other reported methods [16][17][18], the PET reaction of F

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

• [10] (Figure 1), Swern conditions [11][12], PPh3 and CCl4 under basic conditions or by using trifluoroacetic anhydride in pyridine [13]. Other methods involving HF or small fluorinated gaseous compounds at high temperatures have been developed, but are not practical in a standard research laboratory

• synthesis of several glycosyl haloacetimidates and benzyl fluoroacetimidates, with different substituent patterns. The method allows for a larger substrate scope of halonitriles than earlier methods and is easily facilitated by low cost commercially available equipment. Examples of methods for the synthesis

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

• ] and vaccines [15][16][17][18]. That is why new efficient and stereoselective methods for the synthesis of both Galf-containing mono- and oligosaccharide derivatives are highly demanded. It is a well-known fact that galactofuranose form constitutes only 5% in water solution of unprotected ᴅ-galactose

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

• catalytic asymmetric synthesis methods. Only recently, methods for the formation of C–Se bonds have been established for the construction of selenium-containing atropisomers. However, there is no comprehensive review to summarize this great progress. In this paper, the catalytic asymmetric synthesis of

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• compound was synthesized from the Diels–Alder adduct 14 between LG and 1,3-butadiene by two methods – vicinal hydroxylation of the double bond followed by periodate cleavage of the vic-diols and ozonolysis of the double bond. Alternatively, Wagner oxidation of the double bond in adduct 14 by treatment with

• , particularly iridoids. One of the promising methods for ring contraction in the absence of multiple bonds in the six-membered ring of terpenoids was proposed by Grishko et al. [26] (Scheme 6). The key step of 2,3-fragmentation was the cleavage of an enolized C–C bond at a keto group, followed by an

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

• scaffolds. From the standpoint of organic chemistry, it is evident that these compounds can be efficiently converted into a variety of versatile organic intermediates through the application of ring-opening reactions [49][50][51][52]. In addition to the aforementioned useful properties, the current methods

• solvent polarity results in a decrease in rate constants. This phenomenon is attributed to the lower polarity of the transition state in comparison to that of the initial compounds [61]. Furthermore, these methods often require harsh reaction conditions, prolonged reaction times, and laborious

• overlooked [69]. However, these methods are accompanied by the inevitability of long reaction times or the use of toxic organic solvents. Such negative aspects encountered during the synthesis of these compounds prompted us to seek alternative, environmentally benign, renewable, and reusable solvents [70

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

• e) [12]. The second category of synthetic methods relies on more accessible, non-pre-functionalized starting materials and stepwise assembly of the spirocyclic core. This strategy enables the synthesis of functionalized 3H-indoles, which can be further elaborated into structurally diverse products

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• the deep understanding of experienced chemists. Looking ahead, several key challenges and opportunities are apparent. Integrating prior knowledge and transfer learning between chemical domains remains difficult but promising. Improved methods for uncertainty quantification could help identify when

• this field and the exciting opportunities ahead. As methods for adaptive experimentation continue to advance, maintaining focus on effective human–AI collaboration will be crucial for realizing the full potential of these technologies in organic chemistry. This integration of automation, machine

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• to construct a β-lactam, an α-metallated piperidine equivalent, overcoming poor yields and stereoselectivity in traditional methods. Its palladium-catalyzed cross-coupling with 2-bromolycodine via β-lactam C–C cleavage enabled stereoretentive coupling, efficiently synthesizing lycoplatyrine A and its