Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• JMS-T100GCV or a JEOL JMS-T200GC spectrometer. All the reactions were conducted under argon or nitrogen. Materials: Column chromatography was conducted on silica gel (Silica Gel 60 N, Kanto Chemical Co., Inc.). Toluene and N,N-dimethylformamide (DMF) were purified by a solvent-purification system

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

• atmosphere, special precautions, and with isolated yields up to 60% [14][15]. Due to the formation of side products, final purification of the amino derivatives requires the use of either multiple separation techniques, chromatography, or distillation [15][16][17][18] (Scheme 1). Differently from lithium

• MassLynx ver. 4.1 and data analysis was done using Waters OpenLynx browser ver. 4.1. Solvents were commercial HPLC grade and used without further purification. The substrates 2a, 7a, and 8a were commercially available and used without further purification. The substituted β-nitrostyrenes 1a and 3a–6a were

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

• , involving the setup of the reaction, mixing of reactants, reaction workup, product analysis, and product purification. To perform all these basic chemistry tasks effectively, customizable HTE platforms are available from various laboratory instrument manufacturers or can be assembled using a mix of

• perform most tasks in chemical and material synthesis, the hardware currently cannot perform product purification and multistep synthesis continuously. HTE using flow platforms Flow reactions are characterized by a constant flow of reagents and products into and out of the reaction vessel. A flow platform

• products once experiments are performed. Despite this bottleneck, the landscape is evolving, with various practical tools emerging to streamline purification processes. From prepacked silica gel tubes to the precision semipreparative liquid chromatography and the versatile capabilities of various scavenger

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

• 49.8 ppm were used as internal references. Mass spectra were acquired on a JEOL JMS-T100LP spectrometer. Flash column chromatography was performed using a Biotage Isolera flash purification system. Extraction and isolation The EtOAc-soluble material (2.45 g) of the methanol extract (38.06 g) from the

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• HPLC (RP-HPLC), which led to the purification of the known metabolites, ianthelliformisamines A–C (1–3) [7] and aplysterol (8) [13], and four new natural products, ianthelliformisamines D–G (4–7) (Figure 1). This extraction and isolation process was repeated twice to obtain sufficient quantities of the

• contained mixtures of polyamine-type alkaloids, which were combined for further isolation work. The following describes the purification of these fractions. Fractions 34–35 (5.0 mg) were purified by semipreparative phenyl RP-HPLC using isocratic conditions of 70% H2O (0.1% TFA)/30% MeOH (0.1% TFA) for the

• first 10 min, then a linear gradient to 10% H2O (0.1% TFA)/90% MeOH (0.1% TFA) was run over 50 min at a flowrate of 9 mL/min; 60 fractions (60 × 1 min) were collected and resulted in the purification of ianthelliformisamine A (1, 1.0 mg, tR 16 min, 0.010% dry wt). Fractions 38–40 were combined (45.0 mg

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• displaying an arylboronic acid and MIDA ester (22 and 23) gave no reaction, side reactions were observed with a dialkynyl germane (24), and the product derived from azide 25 was unstable to purification. To further demonstrate the compatibility and utility of germanyl alkynes in CuAAC reactions, we applied

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

• yields and used directly in the next step without further purification (Scheme 2). In the case of Boc-protected hydrazones, the reaction must be carefully followed and reacted less than 2 hours in order to avoid the cleavage of the Boc group. The hydrazones 3e and 3f substituted by N-Cbz-ʟ-phenylalanine

• compounds 7e and 7f, no competition with the NH of the phenylalanine was observed. The corresponding tetrahydropyridazines 7a–f were obtained in moderate to good yields (Scheme 5). Concerning compounds 7e and 7f, each diastereomer of the 1:1 ratio mixture could be isolated after purification by flash silica

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• -disubstituted tetrazole-methanesulfonylindole derivatives, with yields ranging from 16% to 55% after purification by column chromatography. Despite some yields being modest, they are deemed reasonable considering the reaction’s structural complexity, atom economy, and the efficiency achieved in terms of time

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• it has been isolated via the lengthy iterative purification process guided by bioactivity. Rediscovery is inevitable based on such a workflow, and this is essentially due to our inability to predict the chemical structure ahead of time. Does this have to be the case? The instructions for natural

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• species. As these modifications proceeded effectively with high yields (>90%) without any taxing purification by chromatography, a simple filtration-based purification was sufficient. This synthetic method enabled a flexible molecular design of the CD-based rotaxane framework in an easy, scalable manner

• six glucose units exist in the usual CD molecules, causing the necessity of the purification step to isolate only the mono-substituted product from the mixture containing others, such as two- or three-substituted species or the starting material (CD) itself. For example, a typical mono-substituted α

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• be volatile to simplify complex purification. Second, the solubility of the neutral host complexes usually needs to be improved by the installation of solubility groups, which must be considered during ligand design. The biggest strength of metallocages and metallocontainers, whether they are

• acetate salt results in a charge-neutral and bench-stable [L2Zn2] metallocontainer. Purification of the complex is achieved by lyophilization which accomplishes the removal of acetic acid as only byproduct of the complexation reaction and DMSO as solvent. The charge-neutral receptor is obtained as a

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• products. These highly stable compounds were isolated after purification on silica gel in good yields (Scheme 2) and characterized by spectroscopic methods. The reaction proceeded with very high Z-stereoselectivity (Scheme 2, compounds 9a–d). In the 19F NMR spectra of crude mixtures, only trace amounts of

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• purification. Ketalization of rac-2 with liquid crystal-like ketone 1 [43] (in toluene) or 2,2-dimethoxypropane 5 (in THF) provided dioxanes rac-3 and rac-4 in 56% and 62% yields, respectively (Scheme 2). Samples of rac-3 and rac-4 were separated by preparative HPLC on a chiral phase. Suitable crystals of all

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• . The reaction of H2A with the diaryliodonium salt in phosphate buffer resulted in the expected arylated conjugate in an hour with a maximum of 98% conversion, yielding sulfur arylated product in 54% isolated yield after purification by HPLC. Additionally, the functionalization of the ketone with a

• high conversions (83–93%) in 1–20 hours. Purification by HPLC yielded the isolated oxime conjugates in excellent amounts. This methodology presents a promising approach for the late-stage variation of proteins and peptides, offering versatility and efficiency in aqueous environments. In addition to

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• being explained by a tedious purification. Interestingly, the methodology was successfully applied to the functionalization of aliphatic hydrazones 1s and 1t and even the hydrazone derived from citronellal 1u. The method was functional group-tolerant to various functional groups (nitro, CN, ester

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• information All commercially available reagents and chemicals were bought from Merck & Co. and utilized without extra purification. The melting points of all synthesized compounds were measured utilizing an Electrothermal 9200 apparatus. 1H and 13C NMR and spectra in CDCl3 and DMSO-d6 solvents were recorded

• purification process must be carried out under the mentioned personal protective equipment. The reaction on a larger scale is carried out under special safety conditions [57][58][59]. 3-(Cyclohexylamino)-2-phenyldibenzo[b,f]pyrrolo[1,2-d][1,4]oxazepine-1-carbonitrile (4a); ethyl 2-(4-chlorophenyl)-3

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• latter were treated, without chromatographic purification, with MsCl (methanesulfonyl chloride), NEt3, and DMAP to give the desired products E-β-43a,b. Similarly, glucosides E-β-43c,d and galactoside E-β-43e were obtained. In contrast to oxoindirubin-N-rhamnoside β-41a, all glycosides were obtained as

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• were purchased from commercial sources (Kanto Chemical Co., Inc. or Fujifilm Wako Pure Chemical Corp.) and used without further purification. Super dehydrated, stabilizer-free THF was used as solvent and purchased from Fujifilm Wako Pure Chemical Corp. DEMO was supplied by Kumiai Chemical Industry Co

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• spectroscopy with 1,2-dichloroethane as the internal standard. After these analyses, isolating the products by column chromatography was attempted. Unfortunately, many products were highly volatile and very non-polar, rendering the purification difficult. As a result, in several cases only little or no product

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• a smooth [1,3]-proton shift reaction with a high chirality transfer, affording the corresponding rearranged products in acceptable yields. Without purification, these products were subjected to acid hydrolysis and the subsequent N-Cbz protection, providing the optically active tetrafluoroethylenated

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• materials (Scheme 1d). The synthetic procedure is achieved using blue light irradiation and bromotrichloromethane (BrCCl3), as a one-pot procedure, minimizing chemical wastes, avoiding purification of intermediates, and simplifying practical aspects. Results and Discussion We have recently published the one

• point, allowing the easy purification of the products. As expected, the reaction conducted in the absence of the carbocatalyst led to the obtainment of 2a with comparable yield (Table 1, entries 3 and 4), demonstrating that 1a is a sufficiently activated substrate for the 3C Ugi-type reaction to occur

• the solvent and using Et3N as additive for the eluent of the chromatography on silica gel. With these improvements, we have demonstrated that the yields are comparable to those obtained with purification on alumina but reaching significantly higher degrees of purity of the final products (see

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• -Flight (TOF) LC–MS. The solvent, toluene, was purchased as dry solvent and applied without further purification. Other reagents, catalysts, ligands, acids, and bases were used as purchased from commercial suppliers. Column chromatography was performed on Merck Silica gel 60 (particle size 63–200 μm

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• purification. All experiments were carried out under argon atmosphere in flame-dried glassware using standard inert techniques for introducing reagents and solvents unless otherwise noted. Suzuki–Miyaura cross-coupling with multihalogenated vinyl ethers 1 To a solution of 1 (1.0 equiv), triphenylphosphine (10

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• -hydroxybenzophenones as efficient UV-protectors. Experimental All chemicals were procured from Sigma-Aldrich (AR grade) and used without any further purification. All solvents were purchased from Merck, and were distilled or dried, wherever applicable, following standard procedures. The organic extracts were dried

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• distilled before use. All other chemicals were used without purification unless otherwise stated. Air- and H2O-sensitive reactions were performed under N2. ASAP-APCI-MS was performed on an Expression MS (Advion) mass spectrometer equipped with an APCI ionization source operated in positive mode. The

• freshly distilled propanal (1, 2.1 mL, 30 mmol) were added to a 50 mL flask. The mixture was stirred at 0 °C for 1 h. The residue was filtered and washed twice with diethyl ether, and the solvent was removed in vacuo. The crude product was used without further purification. EIMS (70 eV) m/z (%): 125 (40

• room temperature. The solvent was removed and the residue was washed twice with pentane and dried under vacuum. The product was used without further purification. Analytical data were identical to those reported earlier. 1-Methylheptyltriphenylphosphonium iodide (5): In a manner similar to [31