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

• 94%, initial reactant concentration of 0.5 mol/L, reaction temperature of 40 °C, molar ratio of reactants at 4.4:1, and a residence time of 12.36 minutes. Keywords: continuous flow; kinetic modeling; nitration; reaction optimization; static mixer; Introduction The demand for high-quality

• ]. The reaction time and temperature were reduced from >2 h and 80 °C in industrial operation to 10 min and 65 °C in the microreactor with high conversion and selectivity. Since O-methylisouronium sulfate can be dissolved in high concentrations of sulfuric acid, it is expected to construct a homogeneous

• homogeneous nitration conditions, our next objective was to eliminate the influence of mass transfer. We assessed the impact of flow rate on the reaction conversion under two distinct mixing scenarios (Figure 2a and 2c). The assessments were performed with reaction temperatures at 30–40 °C to eliminate the

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• = 10.9139(1) Å, c = 24.3668(3) Å, β = 95.601(1)°) and a density of 2.01865 g/cm3. Two units of the cationic XB donor form a dimer, which is bridged via two bromide ions (Figure 2). As usual for DAI salts, two XB axes are found on the elongations of the C–I bonds. On the one trans to the isoxazolium unit

• ), 0.1 M, 135 h at rt, 43%, (b) 1.5 equiv mCPBA, 3.0 equiv TfOH (at 0 °C), (DCM), 0.1 M, 20 h at rt, 85%, (c) 1.0 equiv NaBArF24, (acetone), 0.5 M, 2 h at 50 °C under microwave irradiation, 72%. Gold(I)-catalyzed cyclization of propargylic amide 11 as benchmark reaction for Au–Cl activation. Determined

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

• Pt cathode and a Mg anode in the presence of carbon dioxide induced reductive C(sp3)−O bond cleavage at the benzylic position in diarylmethanol compounds and subsequent fixation of carbon dioxide to produce diarylacetic acids in good yield. This protocol provides a novel and simple approach to

• diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates. Keywords: C(sp3)–O bond cleavage; diarylacetic acid; diarylmethanol; electrochemical reduction; fixation of carbon

• dioxide; Introduction Electrochemical reduction of benzyl alcohol derivatives can induce reductive cleavage of a C(sp3)–O bond [1] at the benzylic position to generate the corresponding benzylic anion species. This protocol has been frequently applied to electrochemical carboxylation [2][3][4][5][6][7][8

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• ) Å, the angle O1–H1–O4 106°; O1–H1···O4A: the H1···O4 distance is 2.82(1) Å, the O1···O4 distance is 3.146(3) Å, the angle O1–H1–O4 101°, Figure 3). Additionally, the packing of these chains in the crystal is caused by the intermolecular C–H···O and N–O···π contact. Catechol 6 in crystal also forms

• 121.6°). In addition, the intermolecular H-bonding is observed between group O2–H2 of molecule A and the thione group C=S of molecule B (the distance H2A···S1B is 2.42(1) Å, the angle O2A–H2A–S1B is 161°). At the same time, for molecule B, there is a hydrogen bond between the O2B–H2B group with the

• 2 at the potential range from −0.50 to 1.60 V (CH3CN, GC electrode, Ag/AgCl/KCl(sat.), 0.15 M n-Bu4NClO4, c = 1 mmol·L−1). The CV curves of 3 at the potential ranges from –0.5 to 1.2 V (curve 1); from –0.5 to 2.0 V (curve 2) (CH3CN, GC electrode, Ag/AgCl/KCl(sat.), 0.15 M n-Bu4NClO4, c = 3 mmol·L−1

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

• new methodology used bench-stable allyl-1,3,2-dioxaborinane (27) in the reaction with preformed crude N-aryl-, N-benzyl- and N-allylimines in the presence of 2–8 mol % of the relatively simple 3,3’-Ph2-BINOL catalyst 3 at 50 °C in a microwave reactor at 10 W irradiation for 1 hour to afford amines 26

• , obtained by a 3,3’-diiodo-BINOL 39-catalysed asymmetric CH(CF3)-homologation of dehydrated vinylboronic acids 40 with trifluoromethyl diazomethane at 40 °C. The resulting enantioenriched transient (α-trifluoromethyl)allylboronic acid diethyl esters 41 were converted into the chromatographically stable 1,8

• boroxine with dramatically increased reactivity towards C=N electrophiles. Because of the small steric size of the (BO2) group, the reaction is highly selective towards (E)-α-trifluoromethyl homoallylic amine 44, which otherwise is difficult to obtain in a regiospecific manner. It has to be noted though

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

• conducted a series of studies. Thus, due to the presence of a furoxan fragment, triazinones 1 can act as NO-donors. To assess their NO-release capability, compounds 1 were kept for 1 hour under physiological conditions (pH 7.4, 37 °C), then Griess reagent was added and studied by spectrophotometry (this

• experiments demonstrated that derivatives 1a–f and 7a–e are thermally stable substances with a melting point range of 150–224 °C (DSC curves are provided in Supporting Information File 1), and could be used as components of functional organic materials. Conclusion In summary, we have developed a convenient

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

• , in this case, the cysteine thiols were derivatized and the cysteine C–S bond was previously described to be susceptible to fragmentation, the fragments containing the thiol provide the information on the structure of the modified amino acid side chain [107][108]. Although the study was focused on the

• . Next, we used the diagnostic ions in a closed search with the MaxQuant search engine. For this purpose, we set two calculation runs searching for peptides carrying a mass offset of 485.3366 on C, K, R, E, D, S, T, or H. The closed search including the diagnostic ions found ≈20% more identified peptides

• of mostly used photo-crosslinking groups. B) Mass spectrometry properties of proteins PTMs, which relate to probe–protein conjugates. C) General concept utilizing linkers to improve searches for protein–probe interactions. Direct and indirect approach to identify protein targets and representative

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• attention. The controlled formation of C–C and C–X bonds in a stereoselective fashion has found extensive application in asymmetric synthesis. Notably, the addition of malonates has attracted significant interest, albeit primarily limited to methyl or ethyl diesters [18][19][20]. The combination of iminium

• , condensation reactions, including the formation of transient C=N bonds, are significantly promoted under ball milling conditions [12][13][14]. It is noteworthy that the application of primary amines for activating cyclic ketones under mechanochemical conditions remains largely unexplored [36]. We aim to fill

• nearly equimolar pairs of diastereomeric products due to the lack of appropriate conditions for resolution among the six tested chiral stationary phases. To our surprise, reactions conducted in the ball mill did not lead to the formation of new C–C bonds, and even after extending the reaction time, a

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• Phong Thai Lauv Patel Diyasha Manna David C. Powers Department of Chemistry, Texas A&M University, College Station TX, 77843, USA 10.3762/bjoc.20.197 Abstract Iminoiodinanes comprise a class of hypervalent iodine reagents that is often encountered in nitrogen-group transfer (NGT) catalysis. In

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

• ). Increasing the reaction temperature negatively affected the efficiency of aziridination: Reactions performed at 30 or 50 °C afforded 3a in 50% and 43% yield, respectively (Table 1, entries 5 and 6). Replacing HFIP with 2,2,2-trifluoroethanol (TFE), which is also a commonly encountered fluorinated alcohol

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

• physical organic chemistry with data-driven analysis techniques, in particular MLR, to gain a greater understanding of the enantioselectivity-determining steps for a C–N coupling catalysed by CPA derivatives (Figure 15A) [143]. Based on their findings that π–π interactions between the catalyst’s triazole

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• method to prepare [D1]-formamides (D–C=O) is through a Leuckart–Wallach reaction with an amine and [D1]-methyl/ethyl formate or [D1]-dimethylformamide [19][20]. Stockmann and co-workers produced [D2]-formamides (N–D, D–C=O) via acid-catalyzed nitrile hydrolysis with HCl and D2O [21]. Thus, using the

• increased the overall yield of the reaction (Table 1, entry 5). In summary, minimal formamide (1–2 equiv), excess [D2]-formic acid, and heating to 170 °C in a microwave reactor for 5 minutes is expected to give excellent yields in good deuteration %. A tentative mechanism to [D3]-formamides is shown in

• [D3]-formamide. The ability to deuterate at benzylic positions is particularly relevant as benzylic C–H bonds are common in biologically relevant chemotypes and moreover appear in approximately 25% of the top selling 200 pharmaceuticals [23]. Benzyl cation stability is a driver of metabolism at these

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

• ) was reacted with the Brønsted acid (X equiv) and the fluorine source (Y equiv) in the solvent (4 mL) at temperature of T (°C) for Z hours. The chemical yield of the desired product, (5,5-difluorohexyl)benzene (2a), was evaluated for reaction optimization by using the 19F nuclear magnetic resonance

• , and the substrate was added to the solution after the electrolysis. Optimized conditions and the result are described in Scheme 2. Namely, the electrochemical oxidation of a 0.3 M Bu4NBF4/CH2Cl2 solution (8 mL) at 0 °C using 32 mA generated and accumulated the EGA as the pool. An electricity of 6.0 F

• /mol based on 0.5 mmol was passed to the solution. In order to suppress the increase of the solution temperature under the electrolysis, the electrolysis was conducted at 0 oC. Then, the solution containing EGA was allowed to react with 1a (0.5 mmol) at 0 °C for 0.5 h, giving the corresponding product

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

• unit allows for spin localization at the 10-position of anthracene through C–C bond rotation, resulting in a tail-to-tail σ-dimer (Figure 1b). The σ-dimer exhibits an equilibrium state between the monomer radical and the σ-dimer in solution, and mechano-stimulus-induced C–C bond fission in the solid

• pathway involving hydrogen abstraction from water yielding 4, and a major pathway involving oxygen addition to the central carbon to afford 1,2-dioxetane (DOT) intermediate. Usually, DOT derivatives are known to readily decompose [38], and this DOT intermediate is also considered to decompose upon C–C and

• formation of a 1,2-dioxetane (DOT) intermediate and decomposition to aldehyde 1 and anthroxyl radical 5 via C–C and O–O bond cleavage. This reactivity is attributed to the predominant localization of an unpaired electron at the central sp2 carbon of the DAntM radical. These findings provide variable

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

• , and osmolarity. The tolerated viscosities (determined for standard conditions: 25 °C, 1 bar) range from 1.4 to about 1000 mPa·s. At concentrations of inorganic ions of up to 602 mM and an osmolarity of 1329 mOsm, small concentrations of thscGAS-sfGFP were still detected. The concentration of

• 1:2) were chosen to increase the amount of salts in the solution. Betaine (Sigma, Darmstadt, Germany) + ethylene glycol (Roth, Karlsruhe, Germany) (molar ratio 1:3) was selected as additional common DES. The DES were prepared by weighting out the substances and stirring at up to 100 °C until liquid

• were taken from the databases Chemistry WebBook by the National Institute of Standards and Technology (NIST) (https://webbook.nist.gov/) at 1 bar and 25 °C, PubChem by the National Center for Biotechnology and Information (https://pubchem.ncbi.nlm.nih.gov/), and GESTIS-Stoffdatenbank by Institut für

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

• was outside the scope of this study. Next, DBA 5 was subjected to the SpAAC with benzyl azide. When two equivalents of benzyl azide were added to a solution of 5 in CDCl3 at a controlled temperature of 30 °C, the reaction slowly proceeded (Figure 2). After 22 h, the original peak ascribed to starting

• recorded on a JASCO FP-8500. All calculations were carried out using the Gaussian 16 program [21]. The DFT calculations were carried out using the long-range and dispersion-corrected ωB97X-D functional [22]. The 6-31G(d,p) basis set was used for H, C, O, and S atoms [23][24]. The solvent effect of CH2Cl2

• , 82.18, 66.30, 53.55, 31.39, 28.42, 25.54, 22.48, 13.98; FTIR ν (cm−1): 2067 (C≡C), 1730 (C=O); MALDI–TOF MS (dithranol, m/z): [M]+ calcd for C62H70N6O8, 1026.53; found, 1026.98. Previously reported regioselective double azide addition to DBA with hexyloxy substituents and molecular design in this study

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

• °C, the reaction efficiency significantly decreased (Table 1, entry 13). Alike 2a, the keto isomer of 3a was the dominant isomer, with a keto/enol ratio of 3:1. Then, we tested the effects of different bases on the reaction and found that the strong bases NaOH and KOH gave 3a in high yield (Table 1

• ether (60–90 °C)/ethyl acetate 60:1, v/v) to give 2a (47.3 mg, 91%). Typical procedure for the preparation of β-keto amides 3 (3a as an example) A mixture of (E)-3-(ethylthio)-1-phenyl-3-(phenylamino)prop-2-en-1-one (1a, 70.8 mg, 0.25 mmol), NaOH (30 mg, 0.75 mmol) and PEG-400 (0.236 mL, 0.75 mmol) in

• organic solution was dried with anhydrous Na2SO4, and the crude product was purified by column chromatography on 30–400 mesh silica gel (petroleum ether (60–90 °C)/ethyl acetate 20:1, v/v) to give 3a (53.8 mg, 90%). Synthesis of α-keto thioesters and β-keto amides. Synthesis of β-keto thioesters 2

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

• solvents Tetrabutylammonium bromide/ethylene glycol (1:3 molar ratio) deep eutectic solvent To 8.0 grams of tetrabutylammonium bromide (TBAB) were added 4.7 grams of ethylene glycol (EG). The resulting mixture was heated to 70 °C until a homogeneous liquid formed. It was stored at this same temperature

• between uses. Choline chloride/ethylene glycol (1:2 molar ratio) deep eutectic solvent To 6.98 grams of choline chloride (CC) were added 6.2 grams of EG and the resulting mixture was heated to 70 °C until a homogeneous liquid formed. It was stored at this same temperature between uses. General Sn/Sn

• flash column chromatography. In between reactions, the tin electrodes were rinsed with DI water and acetone, then polished using diamond polish. This helped prevent buildup on the electrode surfaces. General C/C procedure with TBAB/EG To a 10 mL ElectraSyn 2.0 vial containing a magnetic stir bar were

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• mainly via metal-catalyzed C–N or C–C bond formation. Despite recent advances in the area of remote C–H functionalization, this strategy still requires some pre-functionalization of the starting material or the use of directing groups [28][29][30][31][32]. An alternative strategy is based on aromatic

• mmol) and acetone (1–2 mL) or acetone/CHCl3 (3 mL, 2:1), 60 °C. Conditions B: 1a (0.3–0.5 mmol), 2d,f–h (0.45–0.75 mmol), AcOH (30 mol %), molecular sieves 3 Å (300 mg) and acetone (1–2 mL), 60 °C. Strategies to access meta-substituted anilines. Synthesis of meta-substituted anilines from 1,2,4

• -oxadiazol-5-yl substituted 1,3-diketone 1a. Conditions A: 1a (0.5 mmol), 2a,b (0.5 mmol) and acetone (2 mL), 60 °C. Conditions B: 1a (0.5 mmol), 2c (0.75 mmol), AcOH (30 mol %), molecular sieves 3 Å (300 mg) and acetone (2 mL), 60 °C. Synthesis of meta-substituted anilines from 1,3,4-oxadiazol-substituted

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• members), and cyclopenta-fused derivatives (26 members). These compounds will be strictly organized due to their structures and not due a possible concurrent isolation or even to common names (e.g., graphislactones A, C, E, and G will be treated in different sub-chapters, although graphislactones A and C

• respect seems to be available for alternariol or even for its derivatives. Compounds not containing a fully intact resorcylic acid (e.g., dendrocoumarin (C) [29], urolithin A (D) [30], or polygonumoside B (E) [31]) or containing more than the two hydroxy groups of the resorcylic acid (e.g., unnamed

• -methoxylglucopyranoside] (5) was isolated from Alternaria alternata and its structure was determined by NMR spectroscopy. It showed no antibacterial activity [138]. Lysilactones A–C (7–9) bearing β-glucopyranoside moieties were first isolated from Lysimachia clethroides, where lysilactone B is mentioned in this review

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

• –80%) along with their preliminary photophysical (absorption, emission and time resolved fluorescence lifetime) properties. The condensation reaction for assembling the required DPMs were catalyzed with trifluoroacetic acid (TFA) at 0 °C to room temperature (rt), and the stable dipyrromethanes were

• for diverse applications in future studies. Keywords: condensation; co-timerization; dipyrromethane; Friedel–Crafts acylation; heterocycles; pyrrole; truxene; Introduction The scaffold of truxene (10,15‐dihydro‐5H‐diindeno[1,2‐a;1′,2′‐c]fluorene) and its congeners comprises three fluorene subunits

• derivatives (12, 15, and 17) in controlled manner (with appropriate equivalents of acetyl chloride and aluminium chloride) using one-to-threefold Friedel–Crafts acylation reaction(s) at 0 °C to rt in dichloromethane (DCM) solvent (Scheme 1 and Scheme 2). Subsequent condensation of thus prepared acetylated

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• –C) The percentage of the top ten percentile most potent molecules (‘hits’) in the learning set identified over 100 iterations of active learning by (A) AD-CP and Chemprop (CP), (B) AD-XGB and XGBoost (XGB), and (C) Random Forest (RF) and random selection (Random). (D) Bar charts of the average

• ) highlighting molecules identified in the first 45 iterations for (A) AD-CP, (B) Chemprop (CP), and (C) random selection (Random). Top ten percentile most potent compounds are shown as stars and identified compounds are highlighted in yellow. The number of times a model ‘jumps’ from one cluster to another is

• receptor) highlighting molecules identified in the first 45 iterations for (A) AD-XGB, (B) XGBoost (XGB), and (C) Random Forest (RF). Top ten percentile most potent compounds are shown as stars and identified compounds are highlighted in yellow. The number of times a model ‘jumps’ from one cluster to

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

• regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions – synthesis

• /9.26→9.75/10.50→10.26/10.85 ppm) and become more equivalent (Δδ = 1.39→0.75→0.59 ppm accordingly). The key signal in the 13C NMR spectra is located in the regions 174.04–174.69 ppm (C=S), 151.44–151.86 ppm (C=O), and 170.15–170.91 ppm (C=Se) accordingly. Utilization of reaction products The Biginelli

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

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

• more precise stereocontrol of the reaction [128][129][130][131][132]. Therefore, the difference in enantioselectivity values may be attributed to these electronic effects. Ultimately, the most favourable outcomes were achieved with catalyst C30 at 0 °C, with yields reaching up to 84% and enantiomeric

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

• perfluoroalkyl radical, as a carbon radical, rather than iodine radical can add to isocyanides to form imidoyl radicals. Then, the iodine atom of RFI can trap the imidoyl radicals to give the corresponding 1,1-adducts (R–N=C(I)–RF) in good yields [25][26]. Radical addition of group 16 compounds to isocyanides In

• ]. In the case of aromatic isocyanides, the 1,1-addition reaction is probably more likely to proceed because the C–N double bond of the 1,1-addition product 4 (R = Ar, E = PhS) is conjugated to the aromatic ring, which stabilizes it compared to the corresponding adduct with aliphatic isocyanides

• lack of geometrical isomerization of the C–N double bond of the dithiolation products [32]. The thioselenation product 6’, an imine derivative, can be converted to a β-lactam derivative by [2 + 2] cycloaddition with ketene generated in situ. For example, thioselenation of RNC (R = (EtO)2P(O)–CH2) gave

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

• study, many research groups described a strategy for ortho-C–H functionalization of aryl sulfoxides with various nucleophiles via a cascade reaction of interrupted Pummerer reaction/sigmatropic rearrangement (Scheme 1a) [6][7][8][9][10][11]. A large range of nucleophiles, such as phenols [12][13][14][15

• conditions, a significant amount of degradation products was observed and the yield was rather low. The same result was obtained when the reagent was first added at 0 °C and then heated for one hour under microwave irradiation (Table 1, entry 2). To avoid degradation, the temperature was reduced while the

• 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