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

• emerging approach towards molecular solar thermal (MOST) energy storage [5][6][7][8]. In this context, norbornadienes are employed as well established photoswitches because they provide several favorable photochemical and physicochemical properties [9][10]. In a photochromic intramolecular [2 + 2

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

• -moiety and reprotection with (iPr)2SiHCl afforded 75. The addition of BF3·OEt2 at low temperatures induced the fluorination of the silane protecting group and a follow-up intramolecular hydride transfer (via 76). Afterwards, the introduced fluoride was substituted with Mg(OMe)2 in MeOH and the

• , intramolecular ring opening of epoxide 98 and metathesis led to target 104 with high regio- and stereoselectivity. A novel approach towards C1–C10 fragment of 1 was reported by Kathravath and co-workers (Scheme 11) [87]. From ʟ-ascorbic acid (108), protection of the diol motif and treatment with H2O2, then EtI

• and further treated with Lindlar catalyst and DIBAL-H to afford the alkene and aldehyde motifs of 195, respectively. Oxime formation and oxidation yielded an intermediate nitrile oxide, which underwent an intramolecular [3 + 2]-cycloaddition with the adjacent ethene substituent towards isoxazoline 196

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• ) intermediate, which undergoes intramolecular nucleophilic cyclization (Scheme 15) [54]. This work represents the first synthesis of a compound integrating both helical and axial stereogenic elements, and achieves high diastereoselectivity and enantioselectivity through a cinchona alkaloid-derived squaramide

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• -substituted oxacyclophene 1ad We planned to construct the nine-membered cyclic ether skeleton of 1ad in the final step by an intramolecular Williamson etherification of haloalcohol 2 (Scheme 1). The iodine-substituted Z-alkene moiety of 2 was planned to be introduced through a trans-selective hydroiodination

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• hydrocarbons (PAHs) built from angularly annulated rings – occupy a distinctive niche because their non-planar, screw-shaped architectures generate inherent, configurational chirality [3][4][5]. This helicity originates from intramolecular steric congestion and stabilizing π–π interactions between terminal

• electrochemical arenol activations reported by Waldvogel and co-workers [46]. Subsequent intramolecular dehydrative cyclization furnishes the desired oxaza[8]helicenes 5. The oxidation-potential gap between 3 and 4 and the reactivity of Int-I thus provides a handle to control chemo- and regioselectivity

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

• generates a reactive intermediate I. Subsequent exchange of L1 with benzylamine enables intramolecular nucleophilic attack, leading to transamidation. Transition-metal-free electrophilic activation Since the keteniminium ion, which can be readily generated by electrophilic activation of enolizable tertiary

• generates the imidate-like intermediate Q. Subsequent nucleophilic attack of BuOH on the methyl group of Q leads to transition state R, accompanied by the departure of butyl methyl ether. Further attack of BuOH on the O-protonated amide, followed by an intramolecular proton transfer, furnishes transition

• hydrogen chloride acting as a Lewis acid, enabling nucleophilic attack by the amine to form a tetrahedral intermediate Z. Subsequent intramolecular hydrogen shift, followed by elimination of dimethylamine, affords the protonated transamidation product. In 2021, Lee et al. discovered that carbon dioxide

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• -alkynyl-substituted pyrrolidine nitroxides was studied. These nitroxides have been prepared via intramolecular Huisgen cycloaddition or intramolecular alkylation in 2-pyrazolyl derivatives prepared by Michael addition–cyclocondensation of the corresponding alkynones with hydrazine. The reduction kinetics

• often leads to formation of complex polycyclic systems [17][18][19]. In this study, we aimed to construct rigid tricyclic condensed systems with an integrated nitroxyl radical fragment from 3-substituted 2-ethynylpyrrolidine-1-oxyls. The desired tricyclic nitroxides were prepared via intramolecular

• Huisgen cycloaddition or via one-pot Michael addition–cyclocondensation reaction with hydrazine with subsequent intramolecular alkylation of the resulting pyrazoles. Results and Discussion Synthesis We have earlier reported on the synthesis of 2-alkynylpyrrolidine-1-oxyls 2a–c via addition of the

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

• Scheme 22A). Alternatively, one can imagine an exhaustively oxidised intermediate like 74 undergoing α-ketol rearrangement to directly deliver the hydroxy group at C-6 (acid 75) for intramolecular lactonisation towards pierisketolide A (70). In the biogenesis of euphnerin B (76) and euphomilones A (77

• isomers (128b) of the aldol addition is privileged to undergo intramolecular esterification to give alstoscholarinoid B (125). The configuration of the other isomer 128c has been reportedly isolated already in 2002 by Kuo and Chiang [182]. For alstoscholarinoid A (124) an analogous oxidative cleavage and

• (151) after elimination and a second dehydrogenation reaction. Oxidative cleavage of the newly formed 5,6-olefin towards 151a and intramolecular aldol addition furnishes rhodoterpenoid C (150). Applications of ring-size-altering reactions in the total synthesis of terpenoids Since the seminal works by

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• by intramolecular cyclization to yield a lactone, which undergoes decarboxylation to produce the corresponding azomethine ylide. In our system, we propose this generated ylide reacts with N-substituted maleimides 3a–p such that the transformation predominantly proceeds via the endo-TS, leading to

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

• introduced by Cheong and Altman in 2020 (Figure 10A) [83]. In this study, the authors explored an intramolecular, decarboxylative C–H functionalization of benzylic electrophiles, uncovering a decisive role of the base in governing site selectivity. Computational and mechanistic analyses revealed that only

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

• formation of the cyclic lactone, which predominated under such conditions. These findings suggest that intramolecular attack by the quinolinone OH group, leading to cyclization and formation of pyranoquinolinone, proceeds faster than nucleophilic attack by the external alcohol. Thus, under mild or brief

• efficient reaction progress and facile isolation of pure products, with yields ranging from 65 to 81%. Pyranoquinolines 14a–c can be prepared from acids 11a–c via Fischer–Speier esterification, Steglich esterification, or intramolecular acylation through in situ formation of acyl chlorides. The cyclic

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• , the NH₂ group forms a hydrogen bond with ASP183, and the carboxylate interacts with ASN130 (Figure 3), with additional hydrogen bonds to water molecules. Consequently, intermolecular interactions dominate and override the intramolecular forces responsible for the gauche effect in the isolated molecule

• to negligible Boltzmann populations. Thus, zwitterion formation reinforces the gauche effect, likely through an electrostatic attraction between negatively charged fluorine atoms and the positively charged NH₃+ group, as observed in related systems [25]. Even so, this intramolecular stabilization

• balance shifts, since strong intermolecular interactions – especially hydrogen bonding with amino acid residues – favor a type-II geometry as the predominant bioconformation. Nevertheless, when different conformers engage in comparable intermolecular interactions, intramolecular effects such as the gauche

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• emission energy. Consistent with these trends (Figure 2), compound 1 exhibits nearly identical UV–vis absorption across solvents, while its emission shifts bathochromically with increasing polarity, indicating that the luminescence of 1 arises predominantly from intramolecular charge transfer. In a dilute

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• stable in aqueous solutions at room temperature. Furthermore, we show that an intramolecular hydrogen bond is present in solution, which presumably is a key contributor to the high membrane permeability. Collectively, this physical-chemical profiling of 25CN-NBOH provides guidance to researchers with

• respect to the physiochemical properties and handling of the compound in various research scenarios. Keywords: intramolecular hydrogen bond; membrane permeability; solubility; stability; synthesis; Introduction In recent years, classical psychedelics such as psilocybin and LSD have re-emerged as

• relatively high solubility. Intramolecular hydrogen bonding Previous pharmacokinetic investigations showed that 1 displays high permeability in the MDCK assay (apical–basal 29 × 10−6 cm/s and basal–apical 20 × 10−6 cm/s) [6], a well-established in vitro model for assessing blood–brain barrier (BBB

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• transition dipole moments caused by intramolecular motions, leading to a cancellation of dipole moment or potentially weak magnetic dipole moment. In contrast, 1 wt % PMMA matrices exhibited distinct CPL activity, with the CPL signal showing the same sign as the first Cotton effect in the CD spectrum (Figure

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• -order NLO have high hyperpolarizability (β) values through electron-donor (D) and -withdrawing (A) groups linked by π-bridges in their structures [12][13]. Thus, NLO responses can be tunable by adjusting the strength of the donor and acceptor groups based on the intramolecular charge transfer (ICT

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• to the bromonitroalkene afford the intermediate anion II, followed by tautomerization and formation of anion IV, which undergoes intramolecular nucleophilic substitution of the bromide along the C-alkylation pathway [37][38][39] (Scheme 6). The trans-configuration of the methine protons of 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

• 81 was prepared via a Polonovski–Polish reaction and isomerization, which, when adopting the proper conformation, spontaneously underwent an intramolecular [4 + 2] cycloaddition to construct the unsaturated bridged ring of (±)-keramaphidin B in a single transformation. Subsequently, the iminium ion

• protonation during reduction or an isomerization event. Kinetic translocation of the double bond to the correct position enabled an intramolecular Heck reaction, a transformation originally developed by Fukuyama (Scheme 12) [78]. Hydrogenation of (−)-tabersonine to (−)-decahydrotabersonine by Catherine

• achieved the first total synthesis of the hepta-ring-containing natural product (±)-nominine applying a palladium-catalyzed intramolecular α-acylation and Birch reduction as key steps (Scheme 14) [81][82]. Starting with a simple trisubstituted benzene 97, they obtained the ketal 98 in 39% yield over six

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• -mediated stoichiometric radical reactions Traditionally, the use of Zr complexes in organic reactions had been limited to two-electron processes; however, the first example of a Zr-mediated radical reaction was reported by Oshima et al. in 2001. They reported an intramolecular radical cyclization using

• intramolecular addition to the olefin, affording the cyclized acetal product 4. The reaction proceeded efficiently across a range of substrates bearing various substituents at R¹–R⁴, delivering the desired cyclized products 4a–f in good yields. The proposed mechanism is illustrated in Scheme 1C. Initially

• , affording the corresponding alcohol 28. In contrast, when substrates bearing a benzylic alcohol moiety at the α-position were subjected to the same conditions, the reaction proceeded through radical intermediate 31, which underwent a 1,5-hydrogen atom transfer (1,5-HAT) followed by intramolecular C–O bond

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

• norcaradiene product in the case of benzylation, unlike in the close analogues, is due to a steric repulsion. The structure of norcaradiene 6f was confirmed through single crystal X-ray analysis (CCDC 2495985). Allylation of anion 2 was followed by intramolecular [4 + 2]-cycloaddition in norcaradiene 6g to

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

• Scheme 28D, involving initial generation of a nitrogen-centered radical 165, which undergoes intramolecular addition to the pendant allene to form a vinyl radical intermediate 166. Subsequent interception of 166 by an N–Cl bond furnishes alkenyl chloride 164. 1.4 Reaction of alkenyl metals with chlorine

• anion). Generation of tertiary aliphatic cations and intramolecular trapping with alkenes or alkynes is well known in the context of polyene cyclizations [155]. Building on Johnson’s earlier work (Scheme 48A) [156], Fañanás and Rodríguez developed an intramolecular cationic cyclization strategy to

• systems, with no successful extension to other ring sizes. The proposed mechanism involves initial generation of a tertiary or benzylic carbocation, followed by intramolecular cyclization with a pendant alkyne to furnish a vinyl cation intermediate. This species is postulated to be trapped by the solvent

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

• approaches focus mainly on intramolecular radical cyclizations [42][54][55][56][57][58][59][60][61][62][63], while intermolecular [1][64][65][66][67][68] N–N coupling remains a poorly studied area. In addition to the preparation of azo compounds [69][70], intermolecular N–N coupling reactions are 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

• methyl ester who observed intramolecular proton transfer with partial incorporation of deuterium upon quenching with deuterium oxide. In a different context, the role of the Pd catalyst and the associated ligand was studied in the cross-coupling of the organozinc reagent ent-35 with 3-iodomethylfuran

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

• compositions of antitumor antibiotics of the kigamycin family include the oxazolo[3,2-a]pyridine skeleton [55][56]. To obtain oxazolopyridones containing trifluoromethyl substituents, the syntheses have been proposed, which are based on the intramolecular cyclization of 1-phenyl-2-(4-(trifluoromethyl)piperidin

• at the acyl moiety with the amino group of diamino alcohol 3 to generate a three-component intermediate B (Scheme 4). The latter undergoes intramolecular cyclization involving the C=N bond in two equally probable directions: by adding a free amino group to form a hexahydropyrimidine ring of

• 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

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

• ][8]. However, this is mainly possible in the case of functionalized alkynes, where these intramolecular reactions usually involve other functional groups that are contained in the same intermediate. Among the numerous hydrofunctionalization reactions, hydrothiocyanation has attracted much attention

• , thioethers, disulfides, phosphonothioates, and trifluoromethyl sulfides. Additionally, due to the presence of two electrophilic sites (the sulfur atom and the carbon of the nitrile function), thiocyanates can readily undergo domino-type intramolecular cyclization reactions to form heterocycles. So, if a

• dihydrofurans 3d,e remained comparable to those of 3a,b. Perhaps the yields of salts 2d,e were affected by steric factors hindering the intramolecular cyclization or their stability under the reaction conditions. Using TMS-protected secondary and primary iminopropargyl alcohols 1f,g (due to their instability