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

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• addition to a second molecule of 1. Given the negative results observed for other crotonate derivatives (Scheme 3c), coordination between the Li cation and the two chlorine atoms via proposed transition state D may be crucial not only for diastereoselective control but also for the viability of this step

Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• several different formats exist. CSV also has no formal specification, and different characters and delimiters are used by different applications. Inter_2 ‘are metadata in a machine-readable format?’. Less than a third of shared primary data files have machine-readable metadata content. In addition to the

• structure identifiers. In addition to the trivial naming of compounds that is necessary for a human reader to clearly understand the work, also provide linked non-proprietary and machine-readable identifiers (e.g., SMILES or InChIs and InChIKeys) [50][51] to facilitate machine discoverability and

• ., b.p., elemental analysis, optical rotation), thermochemical data, computational data, structure information, cell culture and bioassay data; and excludes X-ray crystallography. ‘NMR’ refers to those examples where a distinct policy for NMR spectroscopic data is available, in addition to the ‘All data

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• binding Na+ and K+ by oligourea foldamers and macrocycles [37][38][39]. However, in the solid−liquid extraction of Li2SO4 in DMSO, addition of crown ether did not help to increase the extraction efficiency. This is because ion-dipole interactions are negligible in high polar solvent, and Li+ binding is

• observed to be downfield-shifted indicative of anion binding. The relative peak positions of N–H (8.5–13.5 ppm, Figure 3) are consistent with their anion binding affinity and solid–liquid extraction efficiency, PO43− > CO32− > SO42−. In addition, the chemical shifts of 18-crown-6 (3.4–3.6 ppm) are observed

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• developed a magnetically recoverable and reusable Fe3O4 nanoparticle-supported copper(I) catalyst with excellent catalytic efficiency for quinazolinone synthesis [11]. In addition, Cai et al. reported that MCM-41-immobilized tridentate nitrogen-supported copper(I) [MCM-41-3N–CuI] served as a highly

• , entries 14 and 15, 80 and 40% yields). In addition, when the reaction time was reduced, the yields decreased accordingly (Table 1, entries 16−18, 70−94% yields). Finally, when the reaction was carried out under open air, the catalytic activity decreased and only 45% yield of the target product was

• , which acts as a base. Subsequently, I undergoes oxidative addition and complexation with the amidine 2 to generate intermediate II. This intermediate then undergoes reductive elimination to form intermediate III, releasing CS@CuI back into the system. Finally, the coupling reaction between the carboxyl

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• , we report the synthesis of 4-(1-methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones via a reversible transimination reaction between Schiff’ base (C=N) linkage-containing pyrrolidine-2,3-dione derivatives and methylamine with yields of 80 to 92%. In addition to nuclear magnetic resonance

• well as ADMET properties. All compounds satisfied these criteria, indicating favorable oral bioavailability. Molecular docking analysis showed that compounds 5a–e act as ligands for inducible nitric oxide synthase (iNOS), especially with Cys200 and Ser242 via hydrogen bonds. In addition, van der Waals

• -(5-Cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxo-1-pyrrolidinyl)phenyl]propanamide (PHA-533533), a synthetic compound containing a 2-pyrrolidinone ring, has been investigated in cancer treatment (Figure 1) [10]. In addition, molecular docking simulation and in vitro studies have shown that some

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• , various light-, heat-, and acid-induced rearrangements have been reported [35], complicating the distinct structural determination of these compounds. In comparison to published NMR and UV–vis data, formation of neither known species can be assumed with certainty. Last, through addition of mono-carboxylic

• characterized by the mutliplet signal around 7.07 ppm for the olefinic (H1 and H2) and the two pseudo-triplet signals at 5.69 ppm (H3) and 5.64 ppm (H4) corresponding to the bridgehead protons. In addition, a sharp singlet signal assigned to the CH3 protons of the tosyl group is found at 2.42 ppm like for the

• observations made during prolonged irradiation experiments. Due to the thermal instability of O-QC2 noted during the investigation, kinetic experiments for determining the half-life time t1/2 were not conducted. However, the addition of CoII-porphyrin POR allowed for the successful regeneration of the parent O

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• ]. The limited investigation of allene hydrocyanation can be attributed to the significant challenges posed by the two orthogonal π-systems in allenes. These challenges include achieving high regioselectivity and controlling (E)/(Z)-stereoselectivity, as 1,2-addition processes to allenes can generate up

• , the hydride addition of DIBAL-H to allene 1a catalyzed by 5 mol % IPrCuCl as the optimal catalyst selectively generated the allylaluminum intermediate 2a with >98% conversion [30]. Subsequent addition of one equivalent of TsCN to 2a in a single vessel at room temperature proceeded regioselectively

• , achieving complete conversion within 30 min and yielding the desired α-quaternary nitrile 3a in 95% yield. Moreover, no byproducts, such as regioisomeric nitriles or derivatives from over-addition of allylaluminum, were observed. After having established the optimized reaction conditions, the substrate

Carbon-rich materials: from polyaromatic molecules to fullerenes and other carbon allotropes

• Hiroko Yamada and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2025, 21, 798–799, doi:10.3762/bjoc.21.62

• ; polyaromatic molecules; In addition to diamond and graphite, traditional carbon allotropes in our old high-school textbook, new types of carbon allotropes, molecular carbons, were discovered in the last decades. These include fullerenes (1985) [1], carbon nanotubes (1991) [2], and graphene (2004) [3]. Due to

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• that controls reaction selectivity by adjusting voltage or current [13]. Simple synthetic systems in electrochemical methods are limited to electrodes, cells, electrolytes, and power supplies. Today, in addition to the above, light, metallic, and organic catalysts are also used to increase the

• experiments, the oxidation current increased further with the addition of diphenylphosphine oxide to the mixture of Mn(OAc)2 and 2,2-bipyridine. This suggests that 2,2-bipyridine likely influenced the oxidation of Mn(II) and reacted with diphenylphosphine oxide. Further studies have also shown that the

• performed in the presence of TEMPO, the product of TEMPO-P(O)R2 was formed, which showed that the process proceeded through a radical path. In addition, the reaction was carried out in an electrochemical environment with an undivided cell, using graphite and platinum plate electrodes as the anode and