Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• [7][8][9][10][11][12][13][14]. Importantly for our work, it can also act as an equivalent of the unstable hyposulfite (SO22−) ion (Figure 1) [15][16]. The reagent was first used for the preparation of symmetrical sulfones as early as 1971 [17], but interest in the reagent has increased dramatically

• sought confirmation of the structures of the minor and major diastereomers in our own hands. Noting that preparation of sulfides by double conjugate addition of Na2S or NaSH has been widely studied, and that the stereochemical assignments presented therein are in some cases supported by X-ray

• -toluenesulfinate to dibenzalacetone (Scheme 5). Diadducts 25 and 27 were isolated as inseparable 3:2 and 4:3 mixtures of diastereomers, respectively. From these experiments, we observed the following: 1) double conjugate addition of methanesulfinate occurs readily, such that selective preparation of monoadduct 24

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• with a dipolarophile, such as an alkene or alkyne, to form a five-membered heterocycle in one step. Currently, this type of reaction allows for the efficient preparation of bi- and polycyclic fused or spiro-linked structures with multiple chiral centers and high regio- and stereocontrol [1][2][3][4

• chiral metal complexes of Ag(I), Cu(I/II), Zn(II), Ni(II) with ligands of the Segphos, Fesulfos, or Biphamphos type [12][13][14][15]. Such catalytic systems control the enantioselectivity of cycloaddition and allow the preparation of enantioenriched pyrrolidines containing several stereocenters in high

• activity. In 2022, Wang and Teng developed an efficient method for the preparation of enantioenriched derivatives of 3,3-difluoro- and 3,3,4-trifluoropyrrolidines 33 in yields of up to 97% via Cu(I)-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides to 1,1-difluoro- and 1,1,2

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• (3.59) nm; ECD (MeOH) λext (Δε) 208 (+6.25), 256 (−0.08), 282 (+0.26) nm; see Supporting Information File 1 for 1H and 13C NMR data in CDCl3; LRESIMS m/z: [M + Na]+ 381, [M − H]− 357; HRESIMS m/z: [M + Na]+ calcd for C20H22NaO6, 381.1308; found, 381.1307. Preparation and purification of semisynthetic

• DMEM containing 2% FBS and 100 U/mL Pen-Strep. The flask was placed at 37 °C and 5% CO2 for 24 h of starvation. Insert preparation 40 µL of Matrigel (1:40 dilution) was added to each insert, followed by fixing for 5 min under UV light in a biosafety cabinet. The inserts were left to dry overnight in

• the biosafety cabinet. After 24 h, 50 µL of FBS-free DMEM with 100 U/mL Pen-Strep was added to each insert and placed in the incubator at 37 °C and 5% CO2 to rehydrate for 1 h. Cell preparation Medium from the starved cells was aspirated, and the cells were washed with 10 mL of 1× PBS. The PBS was

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• -cryptomeridiol (3). Synthesis of depressin (1), cryptomeridiol (2), and 4-epi-cryptomeridiol (3). a) Synthetic route of 1 starting from casbene (4). b) Preparation of 2,4-nitrophenylhydrazone derivative of 13-ketocasbene (9) for X-ray diffraction. c) Synthetic route of 2 and 3 starting from germacrene A (5

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• . Refer to section 4 in Supporting Information File 1 for more details. The percentages of buried volumes of the C atoms are computed using MORFEUS [34]. Data preparation and hyperparameter optimization Following the methodology by Ree et al. and our previous work [3][10], we use the Optuna framework (v

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• catalysts. Results and Discussion Catalyst preparation First, we prepared Pt‒Fe/DMPSi‒Al2O3 with different Fe/Pt ratios by the simultaneous reduction of Pt and Fe salts in a solution containing dissolved sodium borohydride (NaBH4) and suspended DMPSi [15][30][31][32]. After DMPSi stabilized the resulting

• bimetallic nanoparticles, Al2O3 was added to the mixture, followed by methanol. The resulting solid catalyst was collected by filtration, washed with solvents, and heated twice. Si‒Si bonds in DMPSi were partially oxidized to form Si‒O‒Si bonds during the preparation process, and they became cross-linked to

• Al2O3 to form a stabilized composite support [32]. A plausible scenario for the formation of the bimetallic structure of Pt‒Fe nanoparticles during the catalyst preparation would be the same as that for the formation of Pt–Ni bimetallic structures, and it involves the following steps [33]. Na2PtCl6∙6H2O

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• conditions, (S,S)-2 was the sole AMD product and the formation of the respective mesomeric stereoisomer was negligible. It should be noted that this work is a rare example of catalytic asymmetric synthesis of planar-chiral CpMn(I) half-sandwich complexes [19][32]. Results and Discussion Preparation of

• ). Structures of less-reactive enantiomers in three representative planar-chiral vinylmetallocene substrates in Mo/(R)-L1-catalyzed AMD/KR. Asymmetric metathesis dimerization/kinetic resolution of racemic planar-chiral vinylferrocene/vinylphosphaferrocene. Preparation of racemic planar-chiral vinylcymantrene

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

• process, highlighting its precision and efficiency. Keywords: azides; 8-azidocyclooct-4-en-1-yl 4-nitrobenzoate; DFT; epoxycyclooctane azide; methanolysis; Introduction Organic azides are very important precursors for the preparation and synthesis of various nitrogen-containing compounds, as well as

• methodologies for the preparation of this class of compounds are of considerable interest. Azides have traditionally been used as protected primary amine equivalents. Therefore, in our previous studies, we employed azides containing eight-membered rings as precursors in the synthesis of C8-aminocyclitols [12

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• was first examined, since the ester functions as the synthetic precursor to the corresponding acid used in the preparation of PCP derivatives from PCP [21]. For that, PCP was initially synthesized through the molecular cyclisation of pyrrole with 4-hydroxyacetophenone in methanol in the presence of

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• hope that all readers, whether seasoned experts or newcomers to the field, find as much pleasure and inspiration in these articles as we derived from the preparation and collaboration that brought them to life. We believe that the diverse perspectives and rich discussions encapsulated within these

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

• alkyne 6. Subsequent preparation of the lithium acetylide using n-BuLi, followed by treatment with formaldehyde, afforded propargyl alcohol 3a in 70% yield over three steps. The reaction of 3a with Red-Al generated a vinyl aluminum species, which was then treated with iodine to provide the iodinated Z

• , the treatment with iPrMgBr for preparation of the magnesium alkoxide at highly dilute conditions (10 mM) and sequential cyclization successfully proceeded to provide the C6-iodo-substituted oxacyclophene 1ad in 79% yield. Synthesis of C6-methyl and C6-phenyl-substituted oxacyclophenes The Kumada–Tamao

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• -aminocalix[4]arenes enriched with alkyne or azide functionalities can be readily used as multifunctional platforms to obtain even higher functionalized macrocycles. As an example, they can be used for the preparation of sophisticated supramolecular assemblies with homo- or heterodimeric calixarene cores and

• developed for the preparation of the targeted multifunctionalized calixarenes. Propargylated p-aminocalix[4]arenes Following the published example [9], for the preparation of propargylated p-aminocalix[4]arenes a three-step synthesis strategy was selected, which involved protection of the calixarene

• substitution patterns were selected as the starting materials to enable further preparation of the respective mono-, di- and tetrapropargylated calix[4]arene tetraamines and their derivatives. The silylation of propargyl ethers 1–5 was first attempted using tert-butyldimethylsilyl chloride (TBSCl) and the

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

• ] cycloaddition of azomethine ylides at various vinyl sulfones were well studied [38][39][40][41], a method for the preparation of 3-sulfonylpyrrolidines from β-ketosulfones was previously unknown. We synthesized a number of pyrrolidines 2a–f in 83–97% yield, which were purified by an acid-base extraction (Scheme

• promote Hofmann elimination. To enhance the leaving ability of the nitrogen atom we prepared ammonium salts 3 of the obtained pyrrolidines via treatment with alkyl halides. Since the preparation of quaternary ammonium salts of pyrrolidines is straightforward, we employed a one-pot method for its synthesis

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

• twisted amides have revolutionized amide-bond activation, their preparation often requires multistep synthesis or the installation of strongly electron-withdrawing groups, thereby limiting their broad applicability. Thus, the selective activation and transformation of non-twisted, non-activated amides

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

• sulfonate group, respectively [24]. The 1H NMR spectra of 3a,b,d–f (Zn/CF3COOH system in CD3OD) showed appearance of a singlet of methanesulfonate hydrogens in the region from 2.78 to 3.17 ppm. The NMR spectra were not recorded for 3c because of heavy resinification upon the sample preparation. The

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

• ]. Advances in this area of organic synthesis include the preparation of barbiturates containing spiro-fused cyclohexane, cyclopentane, tetrahydrooxepine, and tetrahydroquinoline moieties via [3 + 2], [4 + 2], and [5 + 2] annulation reactions involving arylidene and alkylidene barbiturates [20][21][22][23

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

• ) systems [56][57][58]. Beyond the conceptual advance, the Mo(0) manifold offers practical benefits in terms of scalability and recyclability [59]. However, the preparation of enantioenriched η2-arene complexes presented unique challenges. In contrast to the Re(I) and W(0) analogues, where resolution of the

• utilization of strained arenes; NICS: nucleus independent chemical shifts [26][27][28]. Bonding and reactivity of η2-coordinated aromatic systems [44][46]. Illustrative selection of η2-coordinating dearomatization agents; MeIm: N-methylimidazole, NHE: normal hydrogen electrode. Preparation, lability and most

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

• (Scheme 3) involved the optimization of a two-step procedure reported previously for their preparation from corresponding anilines and malonic ester [40][41][42][43]. The intermediate N1,N3-bis(4-halogenophenyl)malonamides 1a–c were synthesized from 4-halogen-substituted anilines and diethyl malonate in

• pyranoquinoline and in the open-chain ester (see Scheme 6). Supporting Information Supporting Information File 36: Experimental procedures and analytical characterization of all synthesized compounds. Acknowledgements The authors are grateful to Maria E. Filkina for assistance with the design and preparation of

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• soil. It can potentially serve as a phosphorus source in the syntheses of organic phosphates; however, this approach has not been utilized for the preparation of phosphate esters. In this study, we report the first successful synthesis of phosphate esters using phytic acid as a phosphorus source. Crude

• esterification with alcohols using sustainable biomass-derived phytic acid as a phosphorus source (Figure 2E). This approach can facilitate the development of environmentally friendly phosphate ester production as well as phosphorus recovery and recycling techniques. To date, the preparation of phosphate esters

• A total P analysis was performed according to a test method for industrial wastewater standardized in the Japanese Industrial Standards (JIS K 0102 46.3). Step 1 (preparation of a coloring agent): Hexaammonium heptamolybdate tetrahydrate (300 mg) and antimony potassium tartrate trihydrate (12 mg

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• -functionalization, where a bulkier handle provides the required enantiomerization barrier to screw helical chirality (Figure 1C and D). A straight forward preparation of various carbohelicenes via an organocatalytic enantioselective hydroamination reaction of polyaromatic phenols with diazodicarboxamide derivatives

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

• convenient tool for the preparation of phenols from aromatic ketones, several specific approaches have been developed for the synthesis of hydroxylated heterocycles [30][31][32][33][34]. The deacylation of ketones is also another important direction of their transformation [35][36][37][38]. Dihydrothiophenes

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

• ) and water at 25 ± 0.5 °C. The solutions comprising 0.2 mg/mL of 1·HCl were kept in a temperature-controlled incubator, and samples were measured by HPLC immediately after sample preparation as well as after one and four weeks for the experiments in phosphate buffer and after four weeks for experiments

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

• at different pH values. A) Generalized synthetic scheme for several previous syntheses of 6,6’-dibromoindigo. B) The synthetic scheme for 6,6’-dibromoindigo described in this work. Synthetic scheme for the preparation of 6,6’-dibromoindigo from p-bromotoluene (5). Nitration of p-bromotoluene (5

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

• preparation of sulfinimidate esters remain scarce. For instance, Degennaro and Luisi reported a direct amination strategy using N,N’-disubstituted sulfenamides in alcoholic solvents; however, this method suffered from limited substrate scope [13]. Subsequently, Malacria and co-workers reported an oxidative

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

• reaction of S/R-1 with trimethtylsilylacetylene in toluene (Scheme 1). Subsequent deprotection of the trimethylsilyl (TMS) groups with tetrabutylammonium fluoride (TBAF) afforded the desired ligand S/R-3. The preparation of the target platinum(II) complex was performed by using a similar procedure of other