Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• electropositive halogen bond ability along the σ-hole (C–X···O/N/S, a ≈ 180°) and an electronegative hydrogen bond acceptor perpendicular to the C–X bond (C–X···H, a ≈ 90°) [57][58][59][60]. Such halogen bonds have been detrimental in the understanding interactions of organic halogens in biological systems [61

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• interests, no methods have been described to synthesize both trifluoromethoxylated and phenylselenylated molecules. The introduction of a CF3O moiety into organic molecules remains poorly described in the literature, especially the direct trifluoromethoxylation [44][45][46]. Only few radical

• deselenylation to provide trifluoromethoxylated molecules that can be difficult to access by nucleophilic substitution. These results contribute to the further valorization of the DDPyOCF3 salt (arising from DNTFB/DMAP) as an efficient tool in organic fluorine chemistry. Experimental Typical procedure: Synthesis

• separatory funnel and 10 mL of water are added. The aqueous layer is extracted three times with 10 mL of diethyl ether. The organic layers are combined and washed with 10 mL of water. The organic layer is dried with MgSO4, filtered, and concentrated under vacuum. Compounds 2 are obtained after purification

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• the resultant mixture was stirred at 50 °C for 19 h under the open air. After quenching the reaction with 1 M HCl aq., the mixture was extracted with AcOEt three times and the combined organic phase was washed with brine. Evaporation of the volatiles furnished crude materials which were recrystallized

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• the efficient mixing of organic phases (cyclopentadiene, 1,2-dichloroethane, and MeBu3NCl) and aqueous phases (30% NaOH) and optimized it by the use of a simple homemade “PTFE Raschig ring static mixer” (RRSM). The RRSM is simple in structure, easy to fabricate, inexpensive for many flow reaction

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• triphenylmethanol (1n) was subjected to the electrochemical carboxylation, a small amount of carboxylic acid was obtained as a complex mixture. However, in the 1H NMR spectrum of the organic component after extraction with aqueous base, we observed a singlet at δ 5.55 ppm, which could be assigned to the methine

• B in DMSO solvent. Electrochemical reduction of intermediate B should occur in solution, and this would mean that intermediate B must be dissolved in the solvent used. DMSO is well known as a good solvent for dissolving organic metal salts. In this electrochemical reaction medium, a main counter

• a novel, efficient, facile, and green organic method. Experimental General information 1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded in CDCl3 or DMSO-d6 with a JEOL JNM-ECS400 FT NMR spectrometer. The chemical shifts δ are given in ppm with tetramethylsilane (δ 0 ppm) or DMSO (δ 2.50 ppm

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• ; rearrangement; Introduction Nitrogen-containing organic compounds (sometimes referred to as alkaloids due to their basic properties) are of critical importance in medicinal chemistry because of their unique binding properties to biomolecules [1]. Out of 55 drug candidates, approved by the FDA in 2023, 28 (51

• %) are nitrogen-containing organic compounds, with many featuring amino groups adjacent to a stereogenic centre. Some reports suggest that 75% of all FDA-approved compounds are alkaloids [2]. The industrial production of amines on a million-ton scale underscores the significance of methods for their

• synthetic utilisation [3]. Both, nature and humanity utilise ammonia as the central precursor to introduce nitrogen into organic compounds. Nature achieves this through enzymatic processes, sourcing ammonia from geological origins or directly from the air [4], while humanity relies on the Haber–Bosch

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• Yuri A. Sidunets Valeriya G. Melekhina Leonid L. Fershtat N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Leninsky Prospect, 47, Moscow, Russian Federation National Research University Higher School of Economics 101000, Myasnitskaya str., 20, Moscow, Russian

• thermostable components of functional organic materials. Keywords: molecular hybridization; nitric oxide; nitrogen heterocycles; 1,2,5-oxadiazoles; 1,2,3-triazin-4-one; Introduction Nitrogen heterocycles are a significant and broad class of organic substances included in the structure of various natural

• a 1,2,3-triazin-4-one core. The proposed method is based on tandem diazotization/azo coupling reactions of the corresponding amides (Scheme 1). In addition, application perspectives of thus prepared heterocyclic entities as thermally stable components of functional organic materials or NO-donor drug

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• by high percentage of organic solvent, for example 80% acetonitrile. Yan et al. showed that such biotin–probe–peptides afforded characteristic fragmentation of the biotin linker, thus improving the identification of probe–peptide conjugates in cysteine-profiling experiments [102]. The biotin linker

• conjugates may be carried out using desthiobiotin (DTB) as affinity tag instead of biotin [103][104]. The DTB-tag allows to elute probe–peptide–DTB conjugates from streptavidin beads using a mixture of water, organic solvent – typically acetonitrile (ACN) – and an acid such as formic acid. The desthiobiotin

• –azide (DTB–azide) linker still possesses strong binding to streptavidin (Kd ≈ 1 × 10−11 M), but it can be released by mild washing conditions with organic solvent and low pH (Figure 8C) [105][106]. Similarly, desthiobiotin releases upon HCD fragmentation a set of characteristic diagnostic ions including

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• ]. Despite the prominence of organocatalytic reactions, catalyst development has so far mostly been conducted guided by intuition of skilled organic chemists. Given that organocatalytic reactions are governed by different competing interactions, the influence of a change in molecular structure is often non

• reduce the number of required experiments. As such, these methods contribute to the acceleration of catalyst discovery, for example through high-throughput virtual screening. Predating these computational techniques is the desire to understand and explain experimental outcomes in organic chemistry with

• a major challenge in organic chemistry and restricts the applicability of literature data for statistical modelling [30]. Despite emerging high-throughput experimentation (HTE) pipelines [44][45], large datasets of high-quality are still scarce. While multiple large datasets are available for

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• Organofluorine compounds have attracted great attention in various fields, such as organic materials and pharmaceuticals [1][2][3], because fluorinated compounds sometimes show specific properties [4]. So far, several methods have been developed for the synthesis of fluorinated compounds. Using nucleophilic

• fluorobenziodoxole, are also utilized as F+ equivalents to introduce fluorine atoms into organic molecules. In addition, various trifluoromethylation reagents have been developed so far [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Transition-metal-catalyzed fluorination and trifluoromethylation methods have

• solution of Bu4NBF4/CH2Cl2 containing substrates might also promote the same reactions (Figure 1, reaction 6, electrochemical method). Currently, electrochemistry can be regarded as a promising technique in organic synthesis, because heavy-metal reagents can be avoided for the oxidation or reduction of

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• . Keywords: anthracene; cation; dimerization; radical; reactivity; Introduction Organic radicals have garnered significant attention in various research fields, including catalysis [1][2][3][4], chromophores [5][6][7][8], and as agents in dynamic nuclear polarization [9][10][11][12]. Recently, highly stable

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• established itself as a successful tool in organic synthesis. A particularly fast technique for screening enzymes is the in vitro expression or cell-free protein synthesis (CFPS). The system is based on the transcription and translation machinery of an extract-donating organism to which substrates such as

• osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the

• -physiological conditions further extend the parameter space in which CFPS can be performed. This extension would be highly desirable for a coupled CFPS and enzyme assay, where, e.g., an organic solvent is used to solubilize poorly water soluble substrates for the enzyme. In this study, we therefore aim to fill

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• the field of bioconjugation and materials research. We previously reported a regioselective double addition of organic azides to octadehydrodibenzo[12]annulene derivatives with electron-rich alkyloxy substituents. In order to increase the reaction rate, electron-withdrawing substituents were

• introduced into octadehydrodibenzo[12]annulene. In this report, the synthesis of new octadehydrodibenzo[12]annulene derivatives, regioselective double addition of organic azides, and an application to crosslinking polymers are described. Keywords: annulene; click chemistry; polymerization; strain-promoted

• Amano Institute of Technology, and the Nakatani Foundation. Acknowledgement We thank S. Fukushima (Tokyo Institute of Technology) for assisting with organic synthesis.

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• hydrolysis reactions were carried out in the presence of 3.0 equiv of NaOH. The green approach to β-keto thioesters and β-keto amides avoids the use of harmful organic solvents, thiols and thiolacetates as well as amines, which could result in serious environmental and safety issues. Keywords: α-oxo ketene

• N,S-acetals; β-keto amide; β-keto thioester; dodecylbenzenesulfonic acid; hydrolysis; Introduction In the past decades, the application of easily available and stable α-oxo ketene N,S-acetals as significant synthons has received more and more attention in organic synthesis due to their unique

• efficiently prepared β-keto amides (Scheme 1b, path 5) [41]. Despite great progress, all the reported reactions were performed in organic medium, such as CH3CN, CH2Cl2 and CF3CH2OH, which can result in serious environmental and safety problems. Therefore, the development of an environmentally compliant

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• used, offering an interesting new option for electrochemical allylations. Keywords: allylation; electrosynthesis; eutectic solvent; recycling; tin; Introduction The last several years have witnessed a tremendous resurgence of interest in electrochemistry in the area of organic synthesis [1]. While

• funnel with the aid of 10 mL of deionized (DI) water followed by 20 mL of diethyl ether. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered, and the solvent removed in vacuo to afford the crude product, which was first analyzed by 1H NMR spectroscopy and then purified using

• potential conditions of 2 V with no reference electrode until 2.5 F/mol was passed. Following completion of each reaction, the mixture was transferred to a separatory funnel with the aid of 10 mL of DI water followed by 20 mL of diethyl ether. The organic layer was separated, dried with anhydrous magnesium

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• Joachim Podlech Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Kaiserstraße 12, 76131 Karlsruhe, Germany 10.3762/bjoc.20.187 Abstract In this overview, naturally occurring resorcylic lactones biosynthetically derived from alternariol and almost exclusively produced by

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• ][12][13]. The most promising applications of truxene-based systems have been found in organic photovoltaics (OPVs), dye‐sensitized solar cells (DSSCs), fluorescent probes, organic thin‐film transistors (OTFTs), lasers, organic light emitting diodes (OLEDs), liquid crystals, non-linear optical (NLO

• -centered DPMs (14, 16 and 18), we have first prepared the truxene scaffold 9 from the inexpensive and commercially available 1-indanone (8) using an already reported protocol, as illustrated in Scheme 1 [38]. Moreover, the hexabutylated truxene (HexBT) framework 10, soluble in common organic solvents, was

• also assembled through a literature reported method [38][50]. The reason for accomplishing the butylation was to get good solubility of the system, as the pristine truxene scaffold is insoluble in most of the commonly used organic solvents. Next, we prepared mono-, di- and triacylated truxene

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• organic and medicinal chemists. DHPMs are found in a variety of marine-sourced alkaloids, which are essential for creating biologically active natural products [10]. Some of the DHPM derivatives are also known as functional polymers, adhesives, and fabric dyes [8][12]. In recent decades, the scope of the

• ). Results and Discussion Reaction optimization Over the past two decades more than 300 various catalytic systems have been proposed for Biginelli chemistry, e.g., simple inorganic and organic acids, metal salts, metal oxides, ionic liquids, phosphines, nanocatalysts, organocatalysts, ion exchange resins [1

• Foundation for financial support for the presentation of this work at the 15th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-15, November 20–23, 2023, Kyoto, Japan). In addition, last but not least, we thank all brave defenders of Ukraine that made finalizing this work possible

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• Zsuzsanna Feher Dora Richter Gyula Dargo Jozsef Kupai Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary 10.3762/bjoc.20.183 Abstract Organocatalysis has become a powerful tool in synthetic chemistry

• , providing a cost-effective alternative to traditional catalytic methods. The immobilisation of organocatalysts offers the potential to increase catalyst reusability and efficiency in organic reactions. This article reviews the key parameters that influence the effectiveness of immobilised organocatalysts

• applications in organic chemistry. Keywords: asymmetric synthesis; catalyst recycling; heterogenisation; organocatalysis; solid support; Introduction Organocatalysts are small molecules that do not contain a metal atom in the reaction centre and are able to increase the speed of reactions. They have proven

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• reagents, and are widely used in organic synthesis. On the other hand, the use of isocyanides in reactions with heteroatom radicals is limited. However, the reaction of isocyanides with heteroatom radicals is a promising synthetic tool for the construction of nitrogen-containing organic molecules modified

• reaction of carbon radicals with isocyanides generates imidoyl radicals as key active species [12], and addition and cyclization reactions using these radical species are useful in synthetic organic chemistry, especially multicomponent synthesis. If various functional groups can be appropriately attached

• metal complex or functional dye as a photocatalyst (PC) [19][20]. Recently, some important reviews summarize and discuss the use of method 3 in synthetic organic chemistry [21][22]; in contrast, there is little detailed and coherent literature on the overall research trends regarding the latest research

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• , sigmatropic rearrangements have established themselves as robust and versatile tools for many transformations in organic synthesis [1][2][3]. They were widely employed with a wide range of substrates. With a peculiar type of scaffold, S-perfluoroalkyl aryl sulfoxides, in 2009, we were the first to demonstrate

• reaction time was increased with twice the number of equivalents of acetonitrile (−15 °C to rt, for 12 hours, entry 3 in Table 1) without any significant improvement in the yield. As previously reported, the use of an organic base can improve the yield of this reaction [26][38][40][48]. Therefore, we

• conditions (Table 1, entry 9). Other organic nitrogenous bases were tested (Table 1, entries 10–12). Et3N gave nearly the same result, while DBU seemed less efficient. The use of the inorganic base K2CO3 resulted in poor outcomes. With the optimized conditions in hand, a scale-up was successfully performed

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• interface, and a wide range of analysis tools for studying complex biomolecular systems. AMBER provides various force fields, specifically optimised for simulating biological molecules, as lipids (lipids21) [57], proteins (ff14SB) [58], water molecules (TIP3P) [59], general organic molecules (gaff2) [60

• -simulation analysis. It is possible to use different force fields that include GROMOS96, GROMOS53A6, and GROMOS54A7, which are suitable for simulations of biomolecules, organic compounds, and a wide range of solvents (https://www.gromacs.org/index.html). Despite several carbohydrate-specific force fields

• code by hundreds of times. AutoDock 4 comprises two main programs: autodock handles ligand docking by aligning it with precomputed protein grids, while autogrid generates these grids. The grids can also assist organic chemists in designing better binding molecules (https://autodock.scripps.edu/). 2

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• Rita S. Alqubelat Yaroslava A. Menzorova Maxim A. Mironov Department of Technology for Organic Synthesis, Ural Federal University, Mira St. 19, Ekaterinburg, 620002, Russian Federation 10.3762/bjoc.20.179 Abstract Cage-like microstructures were obtained in two steps by sequential Ugi reactions

• the formation of a double Pickering emulsion using a microfluidic technique. Solidification of this structure and removal of the template resulted in the formation of nonspherical capsules with large openings [13]. The use of a polymer matrix that can swell in an organic solvent made it possible to

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• concatenation of organic elementary steps in a one-pot fashion. Many reviews on general syntheses of pyrazoles have been published [25][26][27][28][29][30][31][32][33][34][35][36][37][38], as well as a few dedicated reviews on MCR synthesis of pyrazole derivatives [39][40][41]. In sensu stricto, multicomponent

• organic synthesis. For instance, hydrazinecarbothioamide (40) can be used to synthesize bisheterocycles. Mohamed et al. were able to combine Hantzsch thiazole and Knorr pyrazole synthesis with this building block. Thiazolyl-pyrazolyl-chromenes 43 were synthesized in good yields from substituted 3

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• double Michael addition of γ,δ-unsaturated-β-keto esters or Nazarov reagents with suitable acceptors such as nitroalkenes or alkylideneazalactones [7][8][9][10]. From the perspective of an active methylene containing organic moiety, curcumin and its analogs serve as inexpensive and readily available

• properties such as anticancer, anti-HIV protease, anti-ageing, anti-inflammatory and anti-oxidant, to name a few [12][13][14][15][16][17][18][19][20][21][22][23]. Considering the fact that curcumin’s uniqueness is associated with its ability to function as a multifunctional substrate in various organic

• , our methodology involves a biphasic reaction medium where the starting material, viz. arylidenemalonate, remains in the organic layer and prevents itself from undergoing saponification because it requires either aqueous or alcoholic (MeOH or EtOH) medium. Furthermore, deprotonation of curcumin