Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• . Trimethylsilyl cyanide (TMSCN) has been used as a sacrificial cyanide source. We found that isocyanide (rather than cyanide) is a preferred coordination to calcium during the catalytic cycle, while the active catalyst prefers a side-on coordination of cyanide. The configuration-determining step is a

• of 9 (for Z- and E-configuration, and for Re or Si side attack) should be more or less equal and the actual stereoselectivity must hence be determined in later stages of the reaction. Ligand sites in the pre-complex 9 form a pseudo-tetragonal pyramid, with isocyanide at the apex. Atoms in the Ca–NC

• provisioning for the following reaction step. Hydrocyanation hence proceeds facially with a barrier of only 10.2 kcal·mol−1 via the configuration-determining TS 9-10 by attack of isocyanide at the imine carbon of hydrazone. If the configuration-determining step would be also rate limiting, experimental

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• is dependent on the configuration of the azobenzene photoswitch (E or Z). In both cases, the E isomers exhibit significantly higher RIP(MeMan) values than the Z isomers, approx. two times higher for 4 and approx. three times higher for 5 (cf. Supporting Information File 1, Table S6). The bis

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• configuration was determined by analyzing the 1H NMR spectrum in the δ = 2.8–1.7 ppm region, which displayed the characteristic diastereotopic hydrogen atoms of this compound, as previously reported by Biava et al. [15]. Unfortunately, the corresponding (2S,4S)-isomer 12b was intractable for isolation (yield

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• meantime, an excellent diastereoselectivity (97:3 dr) was achieved in the decarboxylative cyclization of N-mesylamide 9n possessing an S stereogenic center in the α-position to the nitrogen. Unfortunately, the configuration of the newly formed quaternary stereogenic center in 6n could not be established by

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• of an N–C bond, where the stability of the leaving carbocation is the main factor that affects the rate of this step. Next, intermediate 37 is attacked by the phosphorus compound, giving product 35 with retention of the configuration. This mechanism was confirmed when compound 36a was isolated as

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• % yield. Based on X-ray analysis data the synthesized compound 4a is 2H-furo[3,2-b]pyran-2,7(3H)-dione bearing an enamine fragment at the furanone ring (Scheme 2b). It’s interesting to note that prepared product 4a exists in form of the Z-isomer. This configuration is apparently stabilized by an

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• to determine the role of the squaramide. The relative configuration of the stereogenic centres in compound 5aca was determined by X-ray crystallographic analysis (Scheme 3) [33]; the relative configurations of the other compounds 5 were assigned on the assumption of a uniform mechanistic pathway

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• crystallised in the monoclinic space group P21 with R1 = 0.0285 clearly showing the expected (R)-configuration with a Flack parameter of −0.07(6). Starting from monomethylaniline derivative 7, the synthesis of the final building block was finalised by chlorination [20], Alloc protection and saponification [21

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• spectra [1]. Moreover, the ethylene bridge creates a cyclic 8-membered core, inverting the thermodynamically stability in favor of the Z boat conformation compared to parent azobenzene, which has a stable E configuration [1][2][3][4]. Preceding studies including azobenzene-based photopharmacophores showed

• that, in most cases, the sterically demanding Z configuration is biologically inactive, while the stretched E configuration is biologically active [5][6][7]. Because of the inverted thermodynamic stability compared to azobenzene, the stable Z configuration of the diazocine can be administered and

• subsequently activated with light at the site of illness with high spatiotemporal resolution. Thus, collateral damage in the surrounding healthy tissue can be avoided. In addition, the quantitative thermal back-isomerization from the active E to the inactive Z configuration prevents contamination and

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• that the enantiomeric ratio values in Table 5 correspond to the major anti-diastereomer. The absolute configuration of the significant diastereoisomer obtained in the kinetic resolution of compound 3 was established by chemical correlation with (2R,3S)-1,2,3-triphenylpentan-1-one (19), previously

• of 18 with Raney nickel in ethanol at room temperature gave a 3:1 mixture of anti/syn-19. The absolute configuration of anti-19 is (2R,3S), indicating that in the resolution process, the major enantiomer corresponds to the anti-(3S,4R)-5-oxo-3,4,5-triphenylpentanal. Having established that the major

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• [48]. The review will primarily be referring to axial or α-glycosides as 1,2-cis glycosides except for mannosides where the term β-mannosides will be used for 1,2-cis-mannoside configuration, respecting the complexity and novelty they bring to the world of synthetic glycochemistry. The spanning of the

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• )-5,6,7-trichloro-1,3-tropolone [5] (dashed lines) at the positions of N(1), C(2) and C(9) atoms (hydrogen atoms removed) (Figure 4). While maintaining the general configuration of the molecular framework, there are minor differences in the details of their structures, manifested in the observed distances

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• existence in E configuration. Then, the spin system extends over two overlapping olefinic protons at δH 6.89 (H-6)/6.90 (H-7) proceeding to two olefinic protons at δH 6.38 (dd, J = 15.0, 11.0 Hz, H-8) and 6.56 (d, J = 15.0 Hz, H-9). In addition, the 1H–1H COSY spectrum of 1 (Figure 2) revealed another

• δC 34.2 (C-12) and 29.7 (C-13), respectively. The HMBC correlations (Figure 3) indicated that the side chain in 1 ends as –C(CH3)=CH-CH(CH3)-CH2-CH3 resembling those from farinosones A/B [8] and tenellin derivatives [10][11]. The relative configuration of 1 was elucidated based on its ROESY spectrum

• groups ascribed to H3-14 and H3-15 together with a diastereotopic methylene group at δH 1.25/1.36 (H2-13) confirming the depicted end of the aliphatic sidechain as –C(CH3)=CH-CH(CH3)-CH2-CH3 similar to that in farinosones A/B [8] and tenellin derivatives [10][11]. To establish the absolute configuration

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• has an E,E,E-configuration, while the compound 8a has a Z,E,E-configuration. On the basis of the above experiments and the previously published results [42][43][44][45][46][47][48][49][50][51][52], a plausible reaction mechanism was proposed in Scheme 4 to explain the formation of the various oxindole

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• cyanoacetic ester and acetylacetone. The configuration of the products 4 and 5 was established by bromination of a small amount of these isomeric compounds in CDCl3 (Scheme 6) and subsequent analysis of the mixture by 1H NMR spectroscopy. For the stereoisomers 4, the main product was lactone 22, identified by

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• ring in 159. Based on these findings, a potential reaction pathway was proposed. It starts with a chiral phosphoric acid-supported dehydration of 160 and reaction with the favored configuration of bisindoles 159 to form an allene intermediate Int-38. Proton transfer and subsequent intramolecular

• astounding enantioselectivities. Both, light and organocatalyst proved crucial for the reaction. The photochemical aspect isomerizes the double bond to (Z)-configuration, and CPA stabilizes the structure whilst mediating the cyclization. The wavelength of 405 nm was chosen so that only the starting material

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• stomatocyte configuration. Several critical factors contribute to this transformation. Firstly, the application of osmotic pressure which must be sufficiently robust. This control is notably easier with the addition of PEG, as it swiftly creates a substantial osmotic gradient [19]. Secondly, the vesicle's

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• of five small organic molecules, four oligopeptides, and four oligonucleotides in high purity and impressive yield. Although, in the current configuration, the platform lacks characterization modules and has a lower throughput in comparison to other automated platforms, it does offer a low-cost

• . Using this configuration, the platform can perform a calibration of the reagent and product concentration through a standard addition method. Once the PAT is calibrated, the platform performs dynamic experiments where the concentration of the reagents is ramped to explore the parametric space. Finally

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• significantly blueshifted emission maximum at 392 nm, perhaps as a consequence of a more rigid configuration. As for 7-Br, owing to the electron-withdrawing properties of Br, it displays a blueshifted PL maximum at 383 nm. The emission wavelength of 7-Cz-2 has a slight redshift compared to 7-Cz-1, which may be

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• relative configuration depicted in Scheme 6. Also in 2019, Huang and co-workers reported a bifunctional squaramide-catalyzed [4 + 2] cyclization of benzofuran-derived azadienes 11 and azlactones 15 [29]. This methodology enables the synthesis of benzofuran-fused six-membered heterocycles 20 in yields up to

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• /bjoc.20.267 Abstract A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR

• derivatives exhibit a range of bioactivities, including antibacterial, anticancer, antimalarial, and antiviral effects. Since the discovery of the first psammaplysin derivative, psammaplysin A [4][5], these alkaloids have been recognized as challenging targets for total synthesis. The absolute configuration

• , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• LiOH, followed by a coupling reaction with ʟ-valine methyl ester hydrochloride, to give the corresponding four enantiomerically pure tripeptides 8 with satisfactory yields over two steps (Scheme 6). The absolute configuration (S,S,S) of the isomer 8f was unambiguously assigned by X-ray crystallographic

• configuration of compounds 7e and 7e’ and consequently of tripeptides 8e and 8e’ (see Supporting Information File 1). Next, some preliminary conformational studies were performed. Firstly, the X-ray crystallographic analysis of compound 8f did not show any hydrogen-bond pattern and the global structure of the

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• configuration of the double bond was confirmed using 1H,1H-NOESY spectroscopy. As shown in Figure 2, a correlation between protons of the allyl moiety and the aryl substituent evidenced their spatial proximity in molecule 1c. The absence of a correlation between allyl and vinyl protons additionally supported

• the E-configuration. Spectral–luminescence properties Compounds 1 form colored crystals, from pale-yellow (i.e., 1a) to almost black (i.e., 1h). They are soluble and luminescent in most common organic solvents. Solvatochromism of stilbazole 1c, containing a para-methoxy group, was studied first (see

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• and 219. The authors also considered the transition configuration with the H2O molecule attacking the α-C atom at the front. TBAI-catalyzed hydroxyperoxidation of 1,3-butadienes 220 with aqueous hydroperoxides was demonstrated (Scheme 69) [138]. According to the proposed reaction pathway, the redox