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

• approach to complex molecule synthesis. Despite considerable efforts to develop various catalytic systems, the activation of aromatic C–F bonds often requires high temperatures [1][2][3][4][5][6][7]. Therefore, methods for activating aromatic C–F bonds at ambient temperature remain underdeveloped. We have

• (Scheme 1c). In this study, we demonstrate nickel-catalyzed defluorinative cross-coupling [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] of 2-fluorobenzofurans 1 with arylboronic acids 2 at ambient temperature, with nickelacyclopropanes E serving as crucial intermediates for the

• catalyst, PCy3 (20 mol %) as a ligand, and K2CO3 (2.0 equiv) as a base, the desired arylated naphthofuran 3bb was obtained in 75% yield (Table 1, entry 1). Reducing the reaction temperature improved the yield of 3bb, reaching a quantitative yield when the reaction was performed at room temperature (Table 1

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -workers in 2003 (Scheme 13) [28]. Working in acetonitrile at room temperature, very high yields were obtained with recycling of the catalyst with negligible loss of activity. The reaction is successful also by operating it in ethanol as a solvent under microwave irradiation [29]. More recently, the

• cascade reaction for the preparation of α-alkoxy-N-alkyltriazoles 44 that was developed starting from aliphatic aldehydes, alcohols, TMSN3 as azide source and alkynes (Scheme 33) [52]. The reaction occurs under mild conditions in acetonitrile at room temperature but is inhibited when using aromatic

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

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

• , as temperature is a factor in the van ‘t Hoff formula for osmotic pressure [21]. Additionally, dehydration strengthens polysarcosine chains interactions [16], potentially rendering the membrane too rigid for shape transformation. This means that the heating of the vesicles made with polysarcosine

• addition water – this process was facilitated by the glass-transition temperature (Tg) of the polymer, marking the transition from a fluid to a glassy state. To replicate this methodology, it is important that the Tg of PSar-PBLG is high enough to freeze the different morphologies by water addition. The Tg

• the thermogram unveiled a peak during the initial heating cycle, spanning from 40 °C to 90 °C (Supporting Information File 1, Figure S18). This peak corresponds with the dehydration temperature of polysarcosine, suggesting its role in facilitating subsequent shape manipulation [16]. The assembly of

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

• structures both prior to and following the production of the target compounds. The application of mild heating is crucial to reach full conversion of the starting materials in the times indicated in Table 1. However, conversion to the desired products is also achievable at room temperature over 18 hour

• stirring with minor yield loss. Increasing the heating temperature up to 110 °C does not lead to increased product yields (for more information on the optimization process, see Supporting Information File 1, page S19). The use of diethylenetriamine (DETA) was also investigated to evaluate its impact on the

• CuCl2 2 M solution were added dropwise but rapidly to the vessel. The reaction was monitored by TLC and refluxed at 80 °C in either oil bath or heating mantle for the time indicated in Table 1. General workup procedure of the amino products (1b–8b): Once cooled to room temperature, a 35% solution of

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

• adoption of HTE under batch conditions for optimizing chemical synthesis. However, several challenges arise when MTP are used as reaction vessels. First, the independent control of variables such as reaction time, temperature, and pressure within individual wells is not possible due to the inherent design

• constraints of parallel reactors that share the same MTP. In addition, challenges arise when standard MTP-based reaction vessels are used at a temperature near the solvent's boiling point, as this labware is not enclosed or able to cool the top of the reaction vessel to facilitate reflux conditions. Although

• some research groups have developed custom tools to enable high-temperature reactions, these reactors are currently not commercially available. For an in-depth discussion on the limitations of batch reactors for HTE, we refer the readers to a review by Taylor et al. on chemical reaction optimization [5

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• room temperature yielded partially fused nanographene 3 (20%), with formation of six C–C bonds giving four six-membered rings and two five-membered rings. Performing this reaction at a higher temperature led to a lower yield of compound 3 and the formation of byproducts with lower Rf values on thin

• , such as increasing the amount of DDQ or elevating the reaction temperature in the Scholl reaction of 10, only resulted in complex mixtures. Further attempts to subject 3 to the Scholl reaction conditions did not yield further cyclized products but led to the decomposition of the starting material

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

• fully elucidated by single-crystal X-ray crystallography, which was performed on a Bruker APEX-II CCD diffractometer using graphite monochromated Mo Kα radiation at a temperature of 296 ± 2 K. Crystallographic data were deposited with the Cambridge Crystallographic Data Centre under accession number

• were conducted. UV−vis absorption spectra of 7 in toluene solution at room temperature are shown in Figure 2, and the corresponding data are included in Table 2. The spectra in Figure 2a exhibit two major absorption bands at ≈290 nm and ≈340 nm. The band at around 290 nm might be induced by π→π

• has insignificant effect on the molecular ground state of 7-H. The PL spectra of the PhFlOP-based compounds 7 in toluene at room temperature are shown in Figure 3, and the λem values are included in Table 2. Different emission wavelengths are observed due to the various substituents present in the

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• conducted at room temperature for 20 hours, which resulted in a reduction of the yield for 5aa to 9% (Table 1, entry 5). This result might be due to the reactivity of this hypervalent iodine reagent. Indeed, we have previously observed that the transfer of the benzylamine moiety to carbon-based nucleophiles

• – room temperature. Scope of the primary amine electrophilic reaction of sulfenate salts. Reaction conditions: 4 (2 equiv), NaH (2.4 equiv), 2, degassed DMF (0.055 M). Isolated yields. rt – room temperature; NO – not observed. Electrophilic amination reaction in the presence of TEMPO. Reaction conditions

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• substitution of the terminal phenyl ring with a pentafluorophenyl ring. Thus, as expected, they display a Colhex mesophase over large temperature ranges, with only small differences in the mesophase stability and transition temperatures. Furthermore, the presence of the terminal fluorophenyl group enables a

• , C10F8 (6F-BTPn), on the other. With only four alkoxy chains, these polar “Janus” mesogens [33][44] display a columnar hexagonal mesophase over broader temperature ranges and higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylene counterparts [48], whereas the

• compounds, Gnm, exhibit a rectangular columnar phase (Colrec) also over large temperature ranges from ambient up to 183 and 164 °C, respectively. The unsymmetrically alkoxy-substituted derivative, G48, also displays a Colrec over a similar temperature range. The compounds’ photophysical properties have also

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• bromide in N,N-dimethylacetamide (DMA). Table 1 summarizes the results. The yield of the reaction improved as the temperature was increased from 90 °C to 130 °C (Table 1, entries 1–3). When the reaction was carried out at 150 °C, the yield decreased to 27%. A longer reaction period of 72 h at 130 °C also

• ), tetrabutylammonium bromide (31.7 mg, 0.098 mmol), Pd(OAc)2 (2.2 mg, 10 mol %), and triphenylphosphine (2.8 mg, 10 mol %). The mixture was dissolved in 3.1 mL of DMA and stirring was continued at 110 °C for 24 h. Then, water (3 mL) was added after cooling to room temperature. The product was extracted with

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

• -catalyzed asymmetric inverse electron demand aza-Diels–Alder reaction of 1,3-diazadienes 21 and 3-vinylindoles 61 [47]. After a screening of reaction conditions, chiral phosphoric acid XIV was found to be the best organocatalyst, and by using dichloromethane as solvent at room temperature, 43 different

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

• ; Pseudomonas; Suberea; total synthesis; Introduction The marine environment covers over two thirds of the earth’s surface and it encompasses a wide range of complex ecosystems that are highly variable in their physical attributes including pressure, salinity, temperature, and light availability. Both flora

• /CH2Cl2 at room temperature (17% yield). Subjecting the methoxylated benzaldehyde intermediate 9 to a Doebner–Knoevenagel condensation with malonic acid and pyridine afforded the brominated cinnamic acid analogue 10 in 54% yield [19]. Amidation chemistry using carbonyldiimidazole (CDI) [18] and the

• ground using a Fritsch Universal Cutting Mill Pulverisette 19. The ground marine sponge was extracted at room temperature using an Edwards Instrument Company Bioline orbital shaker set to 200 rpm. Solvents were removed from extracts with a Büchi R-144 rotary evaporator and from HPLC fractions using a

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• not isomerize at room temperature, which is typical for highly sterically congested isoxazoles containing a 3-tert-butyl substituent [26]. The mechanism of such isomerizations of isoxazoles has been previously discussed using DFT calculations [25][26], which revealed the formation of an isoxazole–Fe

• complex, which facilitates the cleavage of the N–O bond and subsequent 1,3-cyclization, ultimately leading to the formation of 2H-azirine. Therefore, the isomerization of isoxazole 1j was carried out at a higher temperature, 82 °C, but after hydrolysis of the reaction mixture, instead of the expected

• azirine dicarboxylic acid 6j, oxazole-4-carboxylic acid 9 was isolated. Apparently, azirine 2j underwent ring opening at higher temperature to nitrile ylide 7, which after cyclization and hydrolysis gave acid 9 (Scheme 3) (cf., e.g. [23]). Next, given that the preparation of 2H-azirine-2-carboxamides from

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• studies using methyl ester sulfoxonium ylide 1a and 2,2,2-trifuoroethyl(mesityl)iodonium triflate salt (2a), as model substrates (see also Table S1 in Supporting Information File 1). Combining these at room temperature in acetonitrile produced 3a in 8% 1H NMR yield (Table 1, entry 1). Repeating the

• was also not effective (Table 1, entry 7; 56% yield), extending the reaction time to 24 hours at room temperature gave 3a in 69% yield (Table 1, entry 8). Other chlorinated, ethereal or polar solvents were also tested under this prolonged reaction time, but none proved better than acetonitrile (Table

•  1, entries 9–12). We attempted to decrease the reaction time by increasing the temperature, but these changes resulted in decreased yields of 3a (Table 1, entries 13 and 14). Surprisingly, when using microwave (MW) heating at 70 ⁰C for 10 min in ACN, product 3a was formed in 74% yield (Table 1

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• the equivalents of [1.1.1]propellane (1) relative to SF5Cl and evaluating the impact on selectivity (Table 1). A 0.1 M solution of SF5Cl in n-pentane was added to a 0.8 M solution of 1 in Et2O at room temperature, and the mixture was stirred for 3 hours prior to 19F NMR analysis. Upon increasing from

• established that [1.1.1]propellane participates in radical-chain reactions (i.e., oligomerization) at room temperature in solution to form unsubstituted [n]staffanes. The origin of this innately controlled oligomerization was then investigated through density functional theory (DFT) calculations. The free

• , we confirmed that a phase transition had occurred following structure determination at 240 K [78][79]. The X-ray data revealed that 3 crystallizes in the centrosymmetric orthorhombic space group Pnma in the high temperature phase (HTP) with cell axes a = 21.56 Å, b = 8.95 Å, and c = 7.28 Å, in

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• under mild conditions in DCM at room temperature. A range of substituents on the aromatic ring were tested with electron-withdrawing groups resulting in lower yields compared to electron-donating groups. The proposed mechanism for the reaction involved formation of a chloronium ion and nucleophilic

• as the bromine source and Bu4NBr as a reaction promoter, racemic brominated pyrrolidines 54 were synthesised from a range of homoallylic sulfonamides 53 in excellent yields under mild conditions at room temperature. A mechanism was suggested by the authors (Scheme 29), whereby ligand exchange on PhI

• [2,3-b]indoles 59 were synthesised in up to quantitative yields under mild reaction conditions at room temperature. A range of other indole derivatives were cyclised in similarly good yields demonstrating the scope of the reaction. Li and Liu reported the bromoamidation of alkenes in 2014 (Scheme 32

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

• trifluoroethanol as the solvent and at room temperature [23][24][25][26]. In the initial reaction, propargylamine served as a bifunctional reagent, with the primary amine group participating in the first step and the terminal alkyne promoting the subsequent heteroannulation. (Scheme 2). As observed in our previous

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• up to 8 h at room temperature. Furthermore, the norbornadienes were transformed quantitatively into their quadricyclane photoproducts by irradiation with green light (520 nm) in the presence of a photosensitizer. Keywords: light energy conversion; photochemistry; photochromism; quadricyclanes

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

• = 20,000), revealing that the average number of penetrated CDs could be controlled from 3 to 125 (theoretical maximum was 227) by adjusting the concentration ratio of α-CD to PEG, the reaction temperature, and the end-capping method (Scheme 4B) [65]. Concurrently, in 2007, Jouini and co-workers reported

• comprising dibenzo-24-crown-8 and multiple dumbbell species bearing secondary ammonium salt moieties on their center (Scheme 5) [69]. These species were completely stable when PF6− was deployed as a counter-anion. Other than that, they degraded under high-temperature conditions. The stability of the pseudo[2

• 80 °C. Additionally, that for a single native α-CD molecule proceeded completely at 60 °C within 2.5 h. Thus, the reaction temperature was confirmed as the key to completing the acylation reaction, probably because of the huge steric hindrance of the densely packed hydroxy groups on the [3]rotaxane

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

• calculated distance from the NOE cross peaks is roughly 2 Å for both contacts. We know that the triazole units can rotate by some degree at ambient temperature based on previous investigations [87]. Thus, dynamic tilting up and downwards of the triazole groups is expected. Molecular dynamics simulations (xTB

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

• carried out without solvent and at room temperature, using copper(II) acetate as the catalyst. The reaction pathway of tert-butyl perbenzoate synthesis from benzyl nitriles 60 involves the formation of intermediate D. The Kornblum–DeLaMare rearrangement of peroxide D gives benzoyl cyanide E, which is

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• , with the tosylate trans to the arene in one (θ2 = 177.8) and trans to the ylid in the other (θ1 = 169.5), which suggests that this isomerisation is fast at room temperature and the position of the anion has no significant effect on the stability of these compounds. This hypothesis is further supported

• spectrometry (MS) and NMR analysis were carried out on aborted TGA runs of compounds 1e, 1i, 1j and 1k that had been held at a constant temperature T1 (50–140 °C, see Supporting Information File 1) under an N2 atmosphere in open pans for 30 min or until a mass loss >5% of the original mass was observed, then

• heated to temperature T2 (136–205 °C, see Supporting Information File 1) until 20–40% mass loss of original weight. Based on this data, the following decomposition mechanism is proposed (Figure 4a): MS, 1H and 31P NMR analysis after heating to T1 showed the presence of (methyloxycarbonylmethyl

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• carbonate was added (300 mg, 2.04 mmol), and the reaction mixture was stirred at 100 °C overnight. After cooling the reaction mixture to room temperature, it was poured into methanol (200 mL), and the resulting precipitate was filtered, then washed with water (150 mL) to give the title compound as a dark

• mmol) and 1-bromooctane (2.12 mL, 12.28 mmol) were dissolved in N,N-dimethylformamide (60 mL). Then, potassium carbonate was added (1.13 g, 8.19 mmol), and the reaction mixture was stirred at 100 °C overnight. After cooling the reaction mixture to room temperature, it was poured into methanol (400 mL

• overnight. After cooling the reaction mixture to room temperature, it was poured into methanol (200 mL), and the resulting precipitate was filtered, then washed with water (150 mL) to give the title compound as a dark solid (600 mg, 71%). 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 8.0 Hz, 2H), 8.63 (d, J = 8.3

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

• group from position 4, and then regioselective vicinal functionalization of the generated aryne. The method's compatibility with halide-substituted aryl compounds enhances its versatility and practicality. Moreover, the completion of reaction within a mere 40 minutes at room temperature underscores its

• aryl donor (Scheme 24) [75]. The reaction worked very well at room temperature under base-free conditions. In this one-pot synthesis of double arylation of naphthols 58, a novel radical precursor, [1,1´-oxybis(2,2,6,6-tetramethylpiperidine)] (59), was employed. This precursor undergoes spontaneous

• of O3-arylated galactosides 64 by reacting benzyl-protected galactoside 63 with diphenyliodonium triflates 16 at room temperature in the presence of potassium tert-butoxide as the base (Scheme 26) [77]. This transition-metal-free approach simplifies the synthesis process. Electron-pushing and