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

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

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

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• -substituted compound 4h. No conversion was observed for starting materials 3g,h containing electron-withdrawing substituents located at the phenylacetylene moiety (products 4n,p). In addition, no conversion was observed for 3-methylaniline (product 4o). The photophysical properties of selected pyrrolo[3,2-d

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• incorporated into cyclization reactions. The iminium species generated from enamides via nucleophilic addition or substitution are capable of engaging in further electrophilic additions or isomerization processes. Exploiting the multiple reactivities of enamides facilitates the development of diverse

• nucleophilic addition or substitution, the resulting iminium ions often undergo direct hydrolysis, preventing further use in a cascade nucleophilic addition. As a result, enamines are not ideal partners in tandem reactions for the synthesis of nitrogen-containing products. As analogues to enamines, the

• iminium intermediates can serve as electrophiles. Due to the presence of an amide, the resulting iminiums from the enamides can be stabilized to take part in the second nucleophilic addition, though direct isomerization of the iminiums to the enamides is also possible (Figure 1). Guided by these

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• computational study to design new PCs to be employed in atom transfer radical polymerization (O-ATRP) [17]. Notably, the sulfur-based structure 2 showed excellent performance for this transformation. One year later, the same research group reported its use in a reversible addition-fragmentation chain-transfer

• surprisingly, 5e showed only traces of 8, even with an E*ox of −1.85 V (Table 2, entry 5). Under the oxidative quenching study, we also evaluated the photocatalytic potential of the new family of D–A compounds in the atom transfer radical addition (ATRA) reaction involving styrene and tosyl chloride (TsCl), as

• results are comparable to those obtained by the same author using the well-established PCs 1 and 3 (Table 3, entries 6 and 7) Next, we wanted to analyze the use of the PCs in reductive quenching mechanisms. For this purpose, we selected the Giese-type addition between the N-Cbz-Pro (12, Eox = 0.95 V vs

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• the benzylic alcohol, a 1,2-Grignard addition and an AcOH-interrupted Nazarov cyclization. Keywords: enantioselective synthesis; interrupted Nazarov cyclization; khayanolide-type limonoids; tetracyclic framework; Introduction Limonoids, a class of tetranortriterpenoids derived biosynthetically from

• essential tertiary alcohol at C1. The β-hydroxylactone moiety (D ring) in 11 could be introduced through an intramolecular aldol condensation [35] of acetate 12. Ultimately, the preparation of 12 could be traced back to aldehyde 14 through 1,2-Grignard addition with an organomagnesium reagent [36] prepared

• at C10 was then introduced via a Michael addition (MeMgBr, CuI) to afford 22 in a yield of 65% (4:1 dr at C10). Initial attempts on the carbonyl 1,2-transposition protocol reported by Dong and co-workers were ineffective [45], leading to premature hydride termination and the formation of alkene 23

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• addition, a sequence of reductive post-assembly modifications aimed at increasing the sp³ character of the pyrazolo[1,5-a][1,4]diazepine core was successfully implemented. Representative diazepine-fused heterocycles. Post-Ugi synthesis of benzodiazepines and heteroaryl-fused diazepines. Synthesis of

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• review systematically examines, how these multidimensional control elements (including ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates) synergize to achieve predictable product diversification. In addition, mechanistic insights are discussed

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• Friedel–Crafts-type addition and protonation to complete ortho-position cyclization. In contrast, para-position cyclization was exclusively achieved through π–π interactions between the electron-rich X-phos ligand and the substrate, compensating for the electron-deficient nature of the aromatic system and

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• to a solution of B4aH, the aromatic proton Ha exhibited continuous upfield shifts, while Hb initially shifted upfield and then downfield upon the addition of 1.5 equiv of C62− (Figure 2b and Figure S8 in Supporting Information File 1). These chemical shift changes indicate the interaction between the