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

• ,8R,11R based on the X-ray single-crystal analysis of its corresponding p-bromobenzoic ester (not shown). Total synthesis of (−)-conidiogenones B–F and (−)-12β-hydroxyconidiogenone C Conidiogenones are unique diterpenoids which possess a highly congested 6/5/5/5-fused framework with four all-carbon

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

• the 13C NMR spectrum. We have succeeded in preparing a single crystal from the oxidation products. Interestingly, the X-ray diffraction analysis [66] showed that the single crystal contained two diastereomers (19/20) with the structures displayed in Scheme 2. Similarly, the DMDO oxidation of

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• products capillosanol and chabranol, respectively [18]. Chabranol was identified to contain a new bridged skeleton through extensive NMR experiments. However, no single-crystal X-ray diffraction analysis was conducted, making the structural determinations not that solid. It showed moderate cytotoxicity

• the structure further, X-ray diffraction analysis of the derivative of bicycle 9 was obtained. This approach established the first total synthesis of chabranol in a concise way through the bioinspired Prins-triggered double cyclization strategy to rapidly construct the bicycle. Total syntheses of

• subsp. brachystachys, and discovered a series of complex natural products named sargalmides A–E [43] (Scheme 7a). To clearly elucidate the complex structures, Yue and co-workers used multiple methods including extensive spectroscopic analysis (NMR, IR and MS), X-ray crystallography, quantum-chemical

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• control of the reaction, while oxygen-bridged heterocycles 4 are formed under thermodynamic control. The purity and structure of compounds 4 and 5 were established by elemental analysis, mass spectrometry, 1H and 13C NMR spectroscopy, and X-ray diffraction study (Figure 1). For example, the 1H NMR spectra

• acids. The reaction under ultrasonication at room temperature yields a mixture of the latter with 5-(2-hydroxyphenyl)-7-hydroxy-2-(methylthio)-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic acids. Molecular structure of compound 4c according to X-ray diffraction data. Thermal ellipsoids

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• and 13C NMR spectroscopy, and by X-ray diffraction study (see Experimental part). The 1H NMR spectra of compounds 5 are characterized by the following signals: a broad carboxyl group proton singlet at 12.10–12.17 ppm, an NH group proton singlet at 7.74–8.02 ppm, an aromatic protons multiplet at 6.52

• shift of the signal in the 198 ppm region, corresponding to the carbonyl carbon of compounds 8, to a stronger field in quinoxalinones 9, where cyclization of the keto group has occurred. The structure of quinoxalinones of type 9 was finally assigned based on X-ray diffraction analysis made for 3-(4-(2

• biologically active quinoxalinone derivatives. Molecular structure of 3-(4-(2-(tert-butylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-5,7-dimethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acid (9e) according to X-ray diffraction data. Known multicomponent reactions of KGA. Ugi reaction involving KGA. Tandem Ugi

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

• aminopentynes 16a–c underwent allylic rearrangement, affording tetrahydropyridines 9 (Scheme 6). The tetrahydropyridine core was confirmed unambiguously by X-ray structure analysis of dinitrobenzamide 9c. More electron-rich acylamides reacted faster and gave less side-products, compared to more electron-poor

• . Conditions screening for copper-catalyzed arylation–cyclization of propargylsilane 7d. Supporting Information Supporting Information File 4: Experimental data, synthesis procedures, 1H and 13C NMR spectra, and X-ray data. Funding This work was supported by the Latvian Council of Science Grant LZP-2023/1

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

• confirmed by X-ray crystallographic analysis. Comparative analysis of the 1H NMR data with authentic samples of the natural heliannuol G and heliannuol H enabled structural revision of these compounds, correcting prior misassignments in the literature [31][32]. Through enzyme-catalyzed asymmetric

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• Road, Hong Kong, China Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China 10.3762/bjoc.21.149 Abstract A series of nitrogen (N)-doped macrocycles was successfully synthesized through palladium-catalyzed arylation. X-ray crystallographic characterization

• introduced. In contrast, when bulky 3,5-bis(trifluoromethyl)phenyl groups were introduced, only inherent chiral macrocyclic products (MC3) were obtained in high yield. Their molecular structures are unambiguously characterized by NMR, mass spectra and X-ray crystallographic characterization. In addition

• characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Single crystals suitable for X-ray diffraction measurements of compounds 3a, MC2, and MC3 were successfully obtained to reveal their molecular structures. In the crystal structure of 3a (Figure 2a), the two pyrene units are nearly

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

• absolute configuration of the piperazine formed, a pure sample of compound 2b derived from (1R,2R)-trans-diaminocyclohexane was crystallized from a chloroform solution resulting in the formation of white crystals suitable for single crystal X-ray diffraction studies. The absolute configuration of the

• purified through flash column chromatography on silica gel to give the isolated pure product. X-ray determined structure of chiral piperazine 2b. Synthesis of vicinal diamines via imino-pinacol coupling in the presence of metal-based reductants. Light-promoted imino-pinacol coupling for the synthesis of

• procedures and physical data for the new compounds, copies of 1H and 13C NMR spectra of the prepared compounds. Acknowledgements The authors thank Prof. A. Puglisi (Università degli Studi di Milano) for valuable discussions. For the single-crystal X-ray diffraction analysis the Unitech COSPECT (Università

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem

• rate of evaporation from a nanolitre solution of analyte encased within oil [33], suitable single crystals were obtained. The X-ray analysis allowed the determination of the relative stereochemistry, as shown in Figure 2. Compound 5a crystallised as a racemic mixture in the space group P21/c. The major

• : ENaCt protocols, X-ray diffraction data for 5a, and NMR spectra for novel compounds. Acknowledgements We would like to thank Craig Robertson (University of Sheffield) and the EPSRC UK National Crystallography Service for access to ENaCt technology and the collection of associated crystallographic data

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• ). Powder X-ray diffraction (PXRD) confirmed that crystallinity was preserved even after complete functionalization of DPG (Figure S8, Supporting Information File 1). To test the catalytic behavior of our amine-based lipophilic MOF catalysts, we chose the Knoevenagel condensation between benzaldehyde and

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• relative configuration (cis or trans) of the substituents. Therefore, the structures of the obtained compounds were determined by single crystal X-ray analysis (Figure 1). Thus, all the obtained derivatives of oxo-rhodanine 6, rhodanine 8 and imidazolone 9 had a cis configuration, while the derivatives of

• would be of help in further drug design of spirocyclic scaffolds. Single crystal X-ray analysis for the compounds 6e (A), 7d (B), 8e (C) and 9e (D). Atoms are shown as thermal ellipsoids at 50% probability. All hydrogen atoms, except the one at the stereogenic center, are omitted for clarity. Synthetic

• . Optimization of the reaction conditionsa. Supporting Information Supporting Information File 22: Experimental part, X-ray data and copies of NMR spectra. Acknowledgements A.A. Korlyukov and A.R. Romanenko are grateful to Ministry of Science and Higher Education of the Russian Federation (Contract No. 075

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• vapour diffusion of hexane into a methanol solution of the compound at room temperature) and their X-ray crystal structural analyses were performed (Figure 2) [33]. In the crystals of rac-1a, a π-type intermolecular interaction between the bromine atom and the benzene ring of the quinolinone was found

• electron pair on the bromine atom and a π* orbital of the quinoline-thione ring, rather than a π-type halogen bonding. Although we attempted the preparation of single crystals of the optically pure form of 2a, unfortunately, crystals suitable for X-ray measurement could not be obtained (2a is chemically

• their spectral data, copies of 1H and 13C{1H} NMR charts of compounds 1–4, chiral MPLC and HPLC chart in compounds 1a,b, 2a, evaluation of rotational barriers of compounds 1a,b, and X-ray crystal data of rac-1a,b, (P)-1a,b, rac-2a (check CIF). Funding This work was partly supported by JSPS KAKENHI (C

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ). The structure of Me-M16 was additionally verified by single-crystal X-ray analysis (the enantiomeric compound (R)-Me-M16 resulting from a separate synthesis was crystallized, see Figure 4). Due to the macrocyclic structure, the two ethylene glycol units directly attached to each dimethylphenyl linker

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

• successfully obtained. Subsequently, the compound was used for the synthesis of zwitterionic polysaccharide A1 (PS A1) precursor, and a clear structural elucidation was applied by using nuclear magnetic resonance and X-ray. Keywords: carbohydrates; capsular polysaccharides; diastereochemistry; glycosylation

• confirming their structure by using X-ray crystallography as direct evidence. Subsequently, the pyruvylated galactose was further applied in the synthesis of zwitterionic polysaccharide A1 (PS A1) precursor. Results and Discussion In the initial experiment, p-tolyl 2,3-di-O-acetyl-1-thio-β-galactopyranoside

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• Centre for X-ray Diffraction Studies, the Centre for Chemical Analysis and Materials, and the Centre for Optical and Laser Materials Research of the Science Park of St. Petersburg State University. Funding This work was supported by Russian Science Foundation Grant No. 23-13-00115.

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• largest cyclic array in the series. The oxidative fusion reaction with [bis(trifluoroacetoxy)iodo]benzene (PIFA) afforded a cyclophane-type aza[5]helicene-incorporated macrocycle, the structure of which was unambiguously revealed by X-ray diffraction analysis. Its optical properties have been investigated

• and 8.98 ppm and five doublet signals due to the heterole β-protons in the range of 6.7–5.8 ppm, along with o-phenylene protons around 7 ppm. Single crystals suitable for X-ray diffraction analysis were obtained from a mixture of acetone/n-hexane and the solid-state structure was successfully

• macrocycle whose structure has been confirmed by X-ray diffraction analysis. Next, oxidation of 4 was attempted using [bis(trifluoroacetoxy)iodo]benzene (PIFA) in CH2Cl2 at −78 °C (Scheme 2). These reaction conditions had previously proven effective for the oxidation of 3 and other o-phenylene-bridged

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• -oxadiazolines [40]. Therefore, single crystal X-ray diffraction analysis is typically used to confirm the structure, as we have applied for the hydantoin/1,2,4-oxadiazoline spiro-compounds 5k (CCDC 2432465) and 5l (CCDC 2432466) (for details see Supporting Information File 1). The effect of the substituents on

• technique. Supporting Information Supporting Information File 10: Detailed experimental procedures, characterization data and X-ray crystallographic details. Funding The synthetic research was funded by the Russian Science Foundation, grant number 24-23-00173. Сell viability tests were supported by the

• Ministry of Science and Higher Education of Russia no. 075-01551-23-00 (FSSF-2023-0006). Single crystal X-ray diffraction analysis study was supported by the RUDN University Scientific Projects Grant System, project №021408-2-000.

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• of NMR spectra. Acknowledgements The authors gratefully acknowledge the Magnetic Resonance Research Centre, Centre for Chemical Analysis and Materials Research, X-ray Diffraction Research Centre of Research Park of Saint Petersburg State University. Funding This work was financially supported by

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• analysis of the isolated products of S–H and N–H insertion was carried out based on spectroscopic data (1H and 13C NMR) and the structures of two representatives were established by using the X-ray single crystal diffraction analysis method. Biological activity (cytotoxicity) of some selected products

• derived from 5-mercapto-1H-tetrazoles was also examined. Keywords: 2,5-dihydro-1,3,4-thiadiazoles; enolizable 5-mercapto-1H-tetrazoles; insertion reactions; thiiranes; thiocarbonyl ylides; X-ray analysis; Introduction Cycloaddition reactions, including 1,3-dipolar cycloadditions, are considered as one

• this product, without contamination with 10k, was feasible. Thioaminal 9i and dithioacetal 10i derived from 1-cyclohexyl-5-mercapto-4H-tetrazole (4b) could be isolated as stable, crystalline products and the postulated structures were unambiguously confirmed by the single crystal X-ray diffraction

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• byproduct and exhibited similar polarity as compound 5. The obtained compounds 3, 4, and 5 were identified using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) (see Supporting Information File 1) as well as single crystal X-ray diffraction analysis (vide infra). Furthermore, the

• ruled out. The structures of compounds 3, 4, and 5 were determined by X-ray diffraction analysis (Figure 2). Mono-olefin 3 and bis-olefin 5 adopt a bathtub-like chiral macrocyclic structure rather than figure-eight conformation. Both compounds crystallize as a racemic pair of enantiomers with P21/c and

• has been confirmed by X-ray diffraction analysis. On the other hand, the treatment of bis-olefin 5 under the same conditions recovered the starting material, which highlights the distinctive role of the carbonyl group for the reductive carbon–carbon-bond formation from 3. Conclusion The Wittig

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• in solution and structurally confirmed via single-crystal X-ray diffraction. It demonstrated the highest CPL performance among the series, with a |glum| value of 3.5 × 10−3 and a photoluminescence quantum yield (PLQY) of 0.31, indicating its potential as a chiral emissive material. Building upon this

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• 2,3-dihydro-1,2-thiazole ring are in the range of 75.3–72.4 ppm and signals of the carbon atom of the cyano group in the range of 117.7–116.6 ppm. The structure of 2,3-dihydro-1,2-thiazole 3aa was additionally confirmed by single crystal X-ray diffraction (Figure 2). According to the X-ray diffraction

• (1.5 mL) was added dropwise. The reaction vessel was removed from the ice bath and the reaction mass was stirred for 10–30 min, then transferred to a silica gel column and the corresponding 2-sulfonyl-1,3-thiazole 3 was isolated. X-ray structure determination of 3aa. Crystal data for C21H21N3O3S2 (M

• final R1 = 0.0584, wR2 = 0.1508 (I > 2σ(I)) and R1 = 0.1081, wR2 = 0.2069 (all data). GooF = 1.027. Largest diff. peak/hole 0.31/−0.40 eÅ−3. The experiment was performed on an automatic four-circle X-ray diffractometer "Xcalibur 3" with a CCD detector according to the standard procedure (Mo Kα

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• was generally accepted that this cyclic ether is planar but this myth was eventually debunked by Luger and Buschmann in 1984 who carried out the first X-ray analysis of oxetane [2] and calculated a small puckering angle of 8.7° at 140 K, which is much smaller than the approximate 30° puckering angle

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• heating process. T90 and CY of [3.3.3]_branch (415 °C and 64 wt %) were lower than those of [3.3.3]_linear because of two-step decay profile (Figure S703a in Supporting Information File 1). All the samples showed broad powder X-ray diffraction (PXRD) patterns with unclear peaks at around 2θ = 11° and 20