Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• DIPEA as an organic base but the yield of 2aa was very low and we observed a range of byproducts, mainly amine addition instead of water (see Supporting Information File 1, 2.2 Preliminary and Additional Experiments, Figures S5 and S6). Afterwards, we evaluated the other crucial parameters for

• dependence on the molar ratio of iodonium salt to isonitrile (Table 1, entries 14–21). In case of excess of the isonitrile we observed multiple addition and formation of oligomerized products which hindered the isolation of the product 2aa (Supporting Information File 1, 2.2 Preliminary and Additional

• that bulky isonitriles effectively shield the radical or cationic centers in intermediates X1 or X2, thereby preventing multiple additions of isonitrile to give the highest yields for benzamides 2be and 2ge among the scope of isonitriles. In the final step of the reaction, the addition of a water

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• reactions, are separately debated. In addition, mechanistic insights into the reaction of heteropolycyclic systems, cycloadditions, and aza-Diels–Alder reactions are provided. This is important because multicomponent, one-pot reactions have gained interest as potentially more economic, efficient, and

• harness their Lewis-acidic and weakly oxidizing properties, respectively. In addition, microwave irradiation increases the reaction rate considerably. Furthermore, the use of a solid Cu(I) catalyst immobilized on an aminated silica support allows for a heterogeneous and cost-effective process, featuring

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• advantages of heterogeneous catalysis, but compared to other approaches, we aimed at eliminating the presence of bimetallic catalysts, the addition of a base [50], and the use of costly perfluorinated protic solvents [48]. In addition, this approach offers improved performance compared to photochemical C–H

• efficiently, affording good-to-excellent yields. The Boc-protecting group proved to be stable under the reaction conditions, underlining the importance of avoiding the addition of acidic additives. Steric hindrance exerted a moderate influence on the reaction, and branched aliphatic amines yielded the

• optimisation, we observed that the amount of CuCl required for regeneration was lower than in the preparation step; the addition of only 50% of the CuCl amount used for the preparation of the fresh catalyst was required to achieve comparable performance. The regenerated catalyst was then used in the optimised

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• yield of 50%. In addition, the reaction furnished bis-olefin 5 in 2% isolated yield which is lower than the estimated yield by 1H NMR measurement of the crude mixture (11%). This is due to the partial loss of the product during purification to remove a trace amount of DBC 2, which was generated as a

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• | value of 1.6 × 10−3. In addition, both 29a and 29b demonstrate redox activity, undergoing reversible formation of radical anions, dianions, and radical cations. The radical cation 29b•+, in particular, exhibits a broad near-infrared (NIR) absorption band extending to 3000 nm, highlighting its potential

• -containing hetero[7]helicene 36a containing a boron–nitrogen coordination site [50]. Its chiroptical properties could be modulated through the addition of tetrabutylammonium (TBA) salts, which transformed the boron center from a trigonal planar to a tetrahedral geometry, thereby enhancing the |glum| from 4.7

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• resistance [1][2][3][4]. In addition to their conventional use, azodyes have unique optical properties, defined by the E/Z isomerization [5][6] and by the tautomeric proton exchange [3][7][8][9][10][11], when a OH or NH group is present on a suitable position in the molecule. Both processes are strongly

• addition of water to acetonitrile (Figure 3) lead to increase of the content of the keto tautomers, but the enol form is still present. As suggested by the theoretically predicted chemical shifts of the tautomeric proton (Table 1), the use of NMR could shed more light on the tautomeric composition in

• equilibrium towards C=O-group-containing structures. In addition, the spectra in the remaining solvents show a single band around 500 nm independent on the nature of the solvent. Obviously, these data cannot be interpreted in the frame of the concept for a tautomeric equilibrium. The rotor in 2 contains a OH

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• analogy with an aza-Michael reaction first with the addition of iminoiodinane accompanied with reorganization of double bonds including attack of the negatively charged sulfur atom on nitrogen with subsequent elimination of iodobenzene as good leaving group. The diversity of the structure of the target

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• extract. The chemical dereplication of the crude extract by high-resolution electrospray ionisation mass spectrometry (HRMS) analysis and online natural product databases (Reaxys [19], AntiBase 2017 [20] and Natural Product Atlas [21]) revealed the presence of unknown molecular ions in addition to the

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• the phenomena [17]. In addition, due to the availability of commercially accessible instruments, the applications of HHP in synthetic chemistry have expanded in the past decades. The studied reactions include hydrogenation [18], the addition of enamines to Michael acceptors [19], enantioselective

• still offered a reasonable increase in rates and thus, in yields. In addition to the synthetic advantages, the benefits HHP offers can also translate to green chemistry. The use of HHP extends the scope of solvent-, reagent- and catalyst-free reactions that significantly reduce workup and waste

• imidazole-based N-heterocyclic carbene (NHC)–CuCl complexes [40]. However, their synthesis is often tainted by the use of toxic reagents and solvents. In addition, when o-phenylenediamine reacts with ketones, the common catalytic methods yield benzodiazepine products [41]. In our case the reaction of o

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• (Figure 2) [10][11][12]. As for the analogy to carbonyls, oxetanes display comparable polarity, spatial arrangement of the oxygen lone pairs and hydrogen-bond-accepting ability. In addition, they possess one major advantage and that is greater metabolic stability: while carbonyl groups are susceptible to

• of the resulting alkene [36]. In addition, this intramolecular etherification corresponds to the 4-exo-tet cyclisation which, in terms of kinetics, is the least favoured n-exo-tet cyclisation mode where n ≤ 7 [37]. Nevertheless, the Williamson etherification still remains one of the most common

• and colleagues published a one-step synthesis of spirooxindole 2,2-disubstituted oxetanes 11 via an unprecedented addition/substitution cascade (Scheme 4) [39]. The protocol reacts readily available 3-hydroxyindolinones 9 with phenyl vinyl selenone (10) in aqueous KOH at room temperature and gives

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• abstracted a hydrogen atom from substrate 1. This HAT process returned the amidyl radical 5 to HRP-1, enabling the continuation of the HAT cycle in synchronization with the photocatalytic cycle. The resulting radical 4 then underwent Giese addition with activated alkenes, leading to the formation of products

• (Scheme 2) [70]. Through a similar oxidative pathway, amidyl radical 13 was generated directly from the amide HRP-2, facilitating a smooth HAT process with substrate 1 while simultaneously regenerating HRP-2. The resulting radical 4 then participated in an addition reaction with radical anion 15. The

• PCET process, involving the oxidation of excited 4CzIPN* and deprotonation by a base. The resulting amidyl radical 20 smoothly abstracted a hydrogen atom from the substrate via a HAT process, generating a radical 4. This C-centered radical subsequently underwent Giese addition with activated alkenes

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• in 1,2-dichloroethane giving PAHs 134–137 in high yields (71–85%). All the new PAHs exhibit characteristics typical for “true” π-extended azulenes, such as azulene-like optical absorption and narrow HOMO–LUMO gaps. In addition, compounds 134–137 show reversible stimuli-responsiveness against the acid

• constructed by condensation of dialdehyde 160 with compounds 161–163 yielding diketones 164–166. Next, diketones 164–166 were subjected to nucleophilic addition reaction by lithiated triisopropylsilyl (TIPS) acetylene, followed by SnCl2-mediated reduction of the intermediate diols. Finally, azulene-embedded

• unexpected deboronization reaction upon the addition of TFA. On-surface synthesis Recently, the field of on-surface chemistry has made significant progress, with the successful development of complex metal-catalyzed on-surface reactions that are not accessible through classical solution-based organic

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• mechanism, control experiments were conducted. The addition of radical scavengers such as BHT and TEMPO significantly inhibited the reaction, confirming the involvement of a radical intermediate. Kinetic isotope effect (KIE) studies showed a KIE of 1.0, suggesting that C–H-bond cleavage was not the rate

• the starting material 28 to yield an alkyl radical intermediate 31. This radical undergoes C=C-bond addition, cyclization, and deprotonation, ultimately leading to the formation of the desired products. Simultaneously, MeOH is reduced at the cathode to release H2, maintaining the electronic balance of

• undergoes a tandem sequence of addition to the C=C bond, cyclization, oxidation, and hydrogen abstraction to yield the final product. In the second pathway, a σ-arylpalladium(II) intermediate I is formed, initiated by the active [PdIIX2Ln] species. This intermediate then undergoes a carbopalladation process

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• 1 suggests starting from aroyl chlorides 2 and 2-methyl-N-benzylbenzothiazolium salts 3 by a condensation transform (Scheme 1). The condensation essentially represents an addition–elimination sequence that starts with the nucleophilic S,N-ketene acetal 4, in situ generated from substrate 3 by

• presumed byproducts in the addition–elimination sequence in the presence of an excess of ethanol as a cosolvent are the ethyl ester formed by Einhorn acylation [7] of the acid chloride under the standard conditions and deep colored polar byproducts (according to TLC detection) that arise from self

• addition, since condensations are affected by the bimolecular addition as an elementary step, special attention to the concentration of the nucleophiles has to be paid. According to Mayr’s nucleophilicity scales [8][9][10], a nucleophilicity parameter N for the specific S,N-ketene acetal intermediate 4 can

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• synthetic step distinguishes them from the less accessible substituted vinylarenes, alkynes, cinnamic and α,β-alkynyl carboxylic acids, as well as vinyl azides. In addition, compared to similar silyl and alkyl enol ethers, enol acetates are more resistant to solvolysis, which prevents unwanted side

• -centered radical from diisopropyl H-phosphonate (2a). In addition, the anion affects the redox properties of the copper ion, and thus the optimal choice is important to achieve both sufficient oxidative properties and catalyst recycling by reoxidation with O2. The employment of Mn(acac)3 and FeCl3, which

• isolated in 77% yield (1.3 g, 4.61 mmol). In order to propose the reaction mechanism, control experiments were conducted (Scheme 4). The reaction is completely inhibited by the addition of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) or BHT (Scheme 4, reaction 1). A BHT-adduct derived from a P-centered

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

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

Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• diol desymmetrization of ent-28 was best achieved with Amano lipase PS (PSL), yielding monoacetate ent-37 (de 99.6%, 93% yield) without the formation of diacetate ent-39. Compound 37 was tosylated using tosyl chloride in pyridine with the addition of DMAP and the resulting product was treated with

• presence of pivaloyl chloride, triethylamine, and lithium chloride to produce compound 71 in 86% yield. Diastereoselective methylation of 71 was achieved by treating it with NaHMDS at low temperature, followed by the addition of methyl iodide, resulting in a diastereomeric ratio greater than 98:2

• compound 85 to produce 84 (Scheme 13). After numerous attempts, it was found that treating 85 with LDA at low temperature followed by the addition of various acids yielded 84 as the minor product, with the product ratio of 85/84 ranging from 2:1 to 3:1. Attempts to influence the stereochemical outcome by

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• ]pyrazine was explored here for phenethylamine and 13 other liquid primary amines. This convenient synthesis involving only addition of liquid amine to starting material, and stirring at room temperature, was found to proceed readily within 6 to 16 h, in generally high yield. Exclusive tele-substitution (8

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• [45]. The ores were obtained in an artisanal way from the Shanono gold deposit in Kano State, Nigeria. The researchers involved in this study used a modified aqua regia solution to digest the ore concentrate, in which hydrochloric acid was replaced by hydrobromic acid. Upon addition of α-CD and KOH

• , there was the formation of the {α-CD·[K(OH2)6]+[AuBr4]−}n complex, leading to immediate precipitation. Isolation of metallic gold from the precipitate was achieved by addition of an organic reducing agent. Moreover, the study optimized the method to yield as much as 69% of gold from the original ore

• . Instead, slow evaporation of the aqueous solvent was required in order to obtain the complex as a crystalline solid. This lengthy isolation made the use of pure β-CD unsuited for industrial application in gold recovery, driving research on co-precipitation methods – these resort to the addition of a co

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• arylated products 3 with triphenylphosphine oxide, this issue does not occur using Pd(dppf)Cl2. The best conditions for the cross coupling were determined to be 5 mol % Pd(dppf)Cl2 as catalyst, 2.0 equiv K2CO3 as base, 1.5 equiv of the required boronic acid and DMF as the solvent. In addition, a minute

• (2R,6S)-11, with only one set of 1H NMR signals, and, hence, one conformer. In addition, for the unprotected (2R,6S)-11 the coupling constants 3J(H6,H5,pro-R) = 12.8 Hz for proton H6 and 3J(H2,H3,pro-R) = 12.9 Hz for proton H2 indicate diaxial couplings, which in return confirms a flip to the more

• reduction product 13 of a Sonogashira–Hagihara cross-coupling reaction. This was synthesised under similar conditions as the Suzuki–Miyaura counterpart 3 utilising the same Pd catalyst, base and solvent. In addition, 10 mol % CuI as a co-catalyst and 2.0 equiv phenylacetylene (12) were used, resulting in

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• at Urbana-Champaign, Urbana, IL, 61801, United States 10.3762/bjoc.21.87 Abstract This study explores the solution- and solid-state assembly of phenylalanine-based hypervalent iodine macrocycles (HIMs) with lithium and sodium cations. The metal cation binding of HIMs was evaluated by addition of

• system [12]. In addition to these covalent bonding interactions, additional secondary bonding (e.g., red-dotted bonds between iodine and oxygen in phenylalanine-based hypervalent iodine macrocycle in benzene system in Figure 1A) can arise in these systems from neighboring atom lone pairs. Secondary

• dynamic assembly and disassembly. Our previous study [18] demonstrates the synthesis of various HIM variants, including a new phenylalanine-based HIM, which show the dynamic behavior of HIM assemblies in solution via addition and removal of anions (Figure 1A). Moreover, due to secondary bonding in the HIM

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• ). Other rare-earth salts, including Y(OTf)3, La(OTf)3, Sm(OTf)3, Tb(OTf)3, Er(OTf)3, and Lu(OTf)3, were also screened, but no better results were observed (Table 1, entries 6–11). In addition, different ligands L2–L4 were evaluated (Table 1, entries 12–14). The enantiomer of product 3aa was obtained in 28

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• applications in the pharmaceutical industry. In addition, innovative synthetic methodologies, including environmentally sustainable approaches [21][22][23], advanced catalytic systems [24][25][26], photocatalysis [27][28][29], and cutting-edge technologies, such as flow chemistry [30][31], have contributed

• the electrophilic triazinedione, releasing DMAP to give ester 15 which reacts with DMAP to afford the active N-acylpyridinium species 16. In addition, N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC·HCl), a common coupling reagent, has been applied for a continuous flow

• active acid chloride 46 to obtain the corresponding ester 44 and amide products 13 and 45 in good yields (Scheme 14) [46]. In addition, this method has successfully been conducted in gram-scale reactions. Cobb and Brittain (2021) reported the amidation of cinnamic acid (7) by applying electrophilic

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• , with particular attention to the 1,2-difunctionalization of olefins by alkyl halides via atom transfer radical addition processes in the presence of amorphous nitrogen-doped carbon dots (Scheme 1a) [20]. In the framework of this research topic, we decided to investigate the use of carbon dots as

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• synthesis of spirocyclic compounds [1][2][3]. The nucleophilicity of isatin at the nitrogen atom allows it to participate in reactions such as alkylation [4], arylation [5], and aza-Michael addition [6][7][8]. However, the products obtained from these reactions are primarily achiral or racemic, and only a