Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• computations were performed to gain insights into the mechanism underlying regioselectivity for the methanolysis of the isomeric epoxides 9 (Figure 3). Detailed mechanistic routes involving all possible intermediates responsible for the regioselectivity step were constructed and the free energy barriers for

• formed in both pathways. Free energy computations indicate that the intermediate 12 is thermodynamically more stable by 4.9 kcal mol−1 compared to intermediate 15. The nucleophilic attack by chloride ion bifurcates into two paths, namely C1- (route a) and C2-attacks (route b) for intermediates 12 and 15

• analysis for the protonated epoxide intermediates 12 and 15, derived from epoxides 9a and 9b, respectively, reveals that the charge differences between the epoxide carbons are not pronounced for either diastereomer, indicating that electronic effects alone are insufficient to explain the observed

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• are not necessarily consecutive and may not be readily dissected. Furthermore, as the reaction intermediates are isomers with mainly similar structural fragments, it is difficult to distinguish them by the usually employed spectroscopic methods because of overlapping signals [22][30][33]. Along these

• almost quantitative (see Supporting Information File 1, Figures S13 and S14). To gain more information about the course of the photoreaction and sequential formation of intermediates, the photoreaction of 1f, catalyzed by flavin 4, was investigated with in situ 19F NMR-spectroscopic analysis. During the

• irradiation, the NMR signals of two intermediates (approx. −114 ppm and −116 ppm) were observed (Figure 3 and Supporting Information File 1, Figure S15), which were assigned to monoquadricyclane 2f2,1 and bisquadricyclane 2f1,2 (Scheme 3, Figure 3). As expected, the quadricyclanes were formed consecutively

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• field of the synthesis of 1. This is especially observable for the synthesis of the 4 heterocyclic key fragments or intermediates obtained during the Eisai process. Here, the major progresses can be registered in terms of enhancing the sustainability of pathways through the removal of metal catalysts

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• routes (Scheme 1) [14][15][18]. Intermediates 5–7 were prepared in a manner analogous to Smalley et al. [14]. The first step in the linker synthesis for Au–(CI-994) involved a monoprotection of nonanedioic acid with a benzyl group to give 5 which proceeded in moderate yield due to the formation of the

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• synthesis uses hydroxyacetophenones as starting material, whose hydroxy groups are first protected by various protecting groups and then reacted with aromatic aldehydes to form the corresponding chalcone intermediates. The chalcones are then oxidized with peroxides, such as H2O2, to give the α,β

• -epoxycarbonyl intermediates. The latter undergo simultaneous deprotection and cyclization by treatment with acid to afford the targeted trans-(±)-taxifolin and its derivatives [19][20][21][22][23][24][25][26][27][28][29][30] (Scheme 1a). Although this synthetic route is efficient, a significant drawback is that

• the construction of the α,β-epoxycarbonyl intermediates requires peroxides, which are not stable, highly oxidative, and potentially explosive. Therefore, this method suffers from risky operation and challenging scale up. The Darzens reaction is a classical method to construct α,β-epoxycarbonyl

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• cyclocondensation products – [1,3]oxazolo[4,5-d]pyrimidines. Subsequent reaction with phosphoryl chloride in the presence of N,N-dimethylaniline converted these intermediates into 2,5-diaryl-7-chloro[1,3]oxazolo[4,5-d]pyrimidines II. The structures of compounds 1–9 were proven and confirmed by 1H and 13C NMR, IR

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• consists in the simultaneous generation of two reactive intermediates: terminal alkene A and N-methylazomethine ylide B, and final [3 + 2] cycloaddition. It was found that the latter approach depends on CH-acidity of the active methylene compounds and performs well with the acidic substrates in the range

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• good to high yields. The authors proposed that a manganese–potassium heterodinuclear alkoxylate complex F, formed from Mn(acac)2(Me2N-Phen), potassium methoxide, and n-butanol, serves as the key catalytic species. The dinuclear complex stabilizes the relevant transition states and intermediates

• corresponding amide products 26 were obtained using only 10−4 mol % Pd(COD)Cl2 in combination with 1-benzyl-1H-1,2,3-triazole (L1). Based on kinetic curves, TEM images, catalyst poisoning experiments, MS identification of intermediates, and EPR spectra of the crude mixture, the authors proposed two kinetically

• of 2 equivalents of TCCA as a chlorinating reagent and 2.5 equivalents of lithium benzoate (LiOBz) as a base, primary amides are converted into the corresponding N,N-dichloroamide intermediates 46, which then undergo smooth nucleophilic acyl substitution with alcohols to afford esters. The substrate

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• operational intermediates, as calculations showed instead a concerted rearrangement towards the tertiary cation 23c to be more likely. From here, ent-kaurene (24) is obtained directly after elimination. The formation of ent-atiserene (25) involves a more dramatic rearrangement to reach the tertiary

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• palladium to aryl halides serving as a prominent example [41]. In addition to such fleeting intermediates, recent decades have seen the emergence of numerous well-defined metal–arene complexes, sufficiently stable to enable systematic exploration of their rich and versatile organic chemistry. η2

• reactivity emerges when the metal binds the arene at a site other than its thermodynamically preferred position, giving rise to fleeting but highly reactive intermediates (Figure 7). Such species are typically inferred from the product rather than observed directly. A defining feature of η2-coordinated

• sulfone complex of W(0) (Scheme 3A) [60]. As established previously [61], protonation of η2-arene ligands bearing electron-withdrawing substituents generates reactive arenium intermediates that react with nucleophiles to furnish disubstituted η2-cyclohexadiene complexes. A second protonation/nucleophilic

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• quantitatively. Although the two-step sequence generally performed well, isolation of malonamides 1a–c was associated with significant material loss, impacting the overall yield. To address this, a one-pot synthesis directly from anilines was developed, avoiding isolation of intermediates. After approximately 4

• diverted from the formation of the kinetically favored pyranoquinolinone intermediates toward thermodynamically controlled alcoholysis, ultimately affording open-chain quinolinone esters. As a result, the transformation efficiently produces the corresponding methyl and ethyl esters 10a–c and 9a–c in good

• alcoholysis under prolonged reflux. This insight resolves a long-standing selectivity issue and transforms a known cascade into a synthetically divergent, operationally simple one-pot process. The selective access to methyl and ethyl esters is synthetically valuable, serving as versatile intermediates for

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• significant effect on the reaction outcome. Thus, there was no formation of oxidized intermediates during transformation. The effect of TEMPO (up to 2.0 equiv) was evaluated on the oxidation reaction, and TEMPO was found to not inhibit the formation of 2-hydroxy-substituted product 2a (Scheme 5, VI

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• advantages of inexpensive starting reagents, operationally simple reactions, and minimal purification of intermediates. Moreover, this work reports the successful sulfonation of 6,6’-dibromoindigo, producing water-soluble derivatives of this historically relevant dye. Keywords: 6,6’-dibromoindigo; dye

• carmine (5,5’-indigodisulfonic acid disodium salt). Results and Discussion In pursuing a new synthesis of 1, we sought to develop a shortened, chromium-free, synthetic approach leading to 1 via intermediates of 3 and 4. Furthermore, we were interested in synthesizing a water-soluble derivative of 1 via

• that the reported synthetic scheme is valuable because it can produce 6,6’-dibromoindigo from an inexpensive starting material using operationally simple reactions without the need for extensive purification of intermediates. Additionally, this work shows that it is possible to sulfonate compound 1

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• versatile intermediates for enantioselective S–C bond formation under mild and metal-free conditions. Keywords: asymmetric synthesis; late-stage functionalization; selective oxidation; sulfenamides; sulfinimidate esters; Introduction Sulfur is a privileged heteroatom in organic chemistry, celebrated for

• interest due to their unique reactivity and value as intermediates in molecular design and medicinal chemistry [5][6][7][8][9][10] (Figure 1). In contrast, sulfinimidate esters, which feature a tetravalent sulfur–oxygen (S(=N)–O) motif, remain a relatively underexplored subclass of organosulfur compounds

• [11][12][13][14]. The highly polarized S–O bond imparts distinctive reactivity, making them promising modular electrophilic intermediates for the construction of complex and functionally rich sulfur–nitrogen architectures [14]. Despite their synthetic potential, general and efficient methods for the

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• hydrogenation of aromatic rings The catalytic hydrogenation of arenes offers a powerful route to disrupt aromaticity and access synthetically valuable intermediates. However, its implementation in strategic synthesis has been hindered by the persistent challenge of controlling selectivity across diverse

• fragment-based screening across a broad substrate set, their method efficiently provides cyclohexane and piperidine frameworks commonly found in bioactive molecules and pharmaceutical intermediates. In the same year, Yu and co-worker described another mild and convenient approach to reduce monocyclic

• also be reduced through hydride-based or electron-transfer pathways, which provide complementary modes of reactivity that are often orthogonal to metal-catalyzed hydrogenation systems. Classical dissolving-metal reductions such as the Birch reduction convert arenes into 1,4-dihydro intermediates via

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

• 1875, Louis Henry extended this transformation to ketone 4 (Scheme 1B) [46]. Exposure to PCl5 gave a mixture of chlorinated intermediates described as 5 and 6, which, upon prolonged treatment with ethanolic KOH, underwent elimination to afford allene 7. Henry also observed that thermal treatment of the

• alkenyl chlorides isolated in purities below 85% (not shown) [59]. Transformations of enols to alkenyl chlorides with phosphorous pentachloride (PCl5): β-Chlorovinyl ketones and esters represent highly versatile intermediates, as the chloride moiety is readily displaced by a wide range of nucleophiles

• also worth noting that as early as 1959, Horner reported the synthesis of 1-chlorocyclohexene in 45% yield from cyclohexanone using PPh3.Cl2 complex (not shown) [65]. In 2005, Kamei reported that alkenyl chlorides could be efficiently prepared from the corresponding alkenyl phosphate intermediates via

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

• 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

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

• intermediate C (path a), or by adding an OH group to generate an oxazolidine ring of intermediate D (path b). The subsequent intramolecular cyclization of intermediates C and D involving a secondary NH group and an ester substituent yields the bicycles 4 and 5, respectively (Scheme 4). In the reactions with

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• corresponding reaction profile for X = -OCH3 has been discussed in our earlier study [34]. Figure 2 and Figure 3 present the free energy reaction profiles for chalcones with X = -Cl and X = -NO2, respectively. Table 1 lists the free energy and potential energy for various intermediates and transition states for

• product). These two pathways are further elaborated below and Table 3 lists the free energies and potential energies for various intermediates and transition states for chalcones with different X = -OCH3, -SCH3, -Cl, -NO2 for the reaction proceeding as per Scheme 4 leading to formation of α,β-ditosyloxy

• . Effect of substituent group present on the migrating aryl ring on relative free energies (G) and relative potential energies (E) of the transition state, intermediates and product for the reaction pathway leading to formation of β,β-ditosyloxy ketones. The energies are reported relative to the reactant

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

• The hydrofunctionalization of alkynes is one of the most effective and convenient ways of synthesizing polysubstituted alkenes [1][2][3][4][5]. Such reactions can also afford more complex products, provided that the vinyl intermediates formed during the reaction undergo further transformations [6][7

• 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

• formation and ratio of the products in contrast to the substituents in the imine fragment. NMR monitoring of reactions (1a/NaSCN/AcOH or 1g/NaSCN/AcOH in MeCN) did not allow to detect any intermediates even when the temperature was lowered to 0 °C. In the 1H and 19F NMR spectra the signals of products 2a

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

• . For intermediates, circles are added with the number of carbon atoms (carbons included in the skeleton, carbon atoms of protecting groups are not counted). We decided to deviate from the originally proposed step-count and will stick to the definition of a reaction step being the sum of all

• -Methylenegermine The total synthesis of (±)-4-methylenegermine (17) was reported by Stork and co-workers in 2017 [22]. It represents an unnatural derivative of germine (20) with an additional methylene unit at C4 that was introduced to increase the stability of synthetic intermediates by avoiding the base

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

• have been also prepared. The synthesis of key intermediates 6 and 7 is presented in Scheme 1. The reaction of sulfonyl chloride 9 with 1,3-benzodioxol-5-amine or 2,3-dihydro-1,4-benzodioxin-6-amine gave sulfonamides 10 or 11, respectively. N-Methylation with methyl iodide via compounds 12 and 13

• intermediates 40‒43 to chloro derivative 44, which was converted with amines to compounds 45 and with methanol to ether 46. Finally, we synthesized related tetracyclic derivatives containing the ethylenedioxy moiety attached to positions 2 and 3 of the dibenzo[c,f][1,2]thiazepine (1) core (Scheme 8). While the

• intermediates 6 and 7. Conditions: i) 1,3-benzodioxol-5-amine (n = 1)/2,3-dihydro-1,4-benzodioxin-6-amine (n = 2), PhNEt2, MeOH, rt, 1 h, 95%/92%; ii) MeI, K2CO3, DMF, 4 h/1 h, 97%/98%; iii) NaOH, MeOH/H2O, reflux, 1 h, 97%/99%; iv) 1. PCl5, DCM, reflux, 8.5 h/9 h; 2. SnCl4, 0–5 °C, 2 h/1 h → rt, 2 h; 76%/84

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• . Therefore, we decided to perform the Mukaiyama hydration on advanced intermediates. Next, a K-selectride-promoted chemo- and stereoselective reduction of the C3 carbonyl of 9 was realized to solely deliver 11 in 85% yield [33]. Then, 11 was subjected to Mukaiyama hydration conditions. Under the Fe(acac)3

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

• (H3PW12O40, HPW) as a catalyst in ethanol under microwave (μw) heating (Scheme 5) [63]. These intermediates were then subjected to the previously optimized Knoevenagel condensation conditions with rhodanine or thiazolidine-2,4-dione (Scheme 6). Notably, the hybrid compounds 9a–d, 10a–d were obtained in good

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

• carbonyl compounds and pharmaceutically relevant intermediates. Moreover, this catalytic system operates under green and sustainable conditions, tolerating a broad range of functional groups and substrate scope, and utilizes low-cost, atom-economical, non-toxic starting materials. Keywords: dual catalysis

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

• ][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