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

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• describes the enantioselective Michael addition of pyrazoline-5-ones to α,β-unsaturated ketones. The enantioselectivity and chemical efficiency of this transformation were achieved with a cinchona-alkaloid-derived primary-amine–Brønsted acid composite [22]. A good demonstration of how organocatalysis

• ]. The enantioselective addition of propargyltrichlorosilane to aldehydes was studied by Prabhakar, Takenaka, and co-workers. This transformation was catalyzed by a biisoquinoline N,N’-dioxide catalyst, which acted as a chiral Lewis base [26]. Torres-Oya and Zurro reviewed the recent developments in

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• through calcium catalysis [8][9][10]. Asymmetric synthesis has also been achieved via, e.g., 1,4-addition and [3 + 2] cycloaddition of 3-tetrasubstituted oxindoles with a calcium Pybox catalyst [11][12], or through enantioselective Friedel–Crafts and carbonyl–ene reactions [13]. Since the pioneering

• cyanide source. This observation complies with the results from the computational study (Figure 2). In addition, some TMSCN is consumed together with an amount of BINOL phosphate through the probably parasitic formation of catalytically inactive trimethylsilyl phosphate 3a, which we were able to

• our previous work [45], we carried out the enantioselective hydrocyanation of hydrazones using Ca–BINOL phosphate complex 6 at −10 °C in DCM for 72 h. In addition to those reaction conditions, we initially used t-BuOH as an additive [45]. The Ca–BINOL phosphate complex 6 was prepared in situ by

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• into tetrahydroquinoline (THQ)-based 6-6-4-membered ring systems through a combination of nucleophilic addition and borate-mediated [2 + 2] photocycloaddition, offering a catalyst-free approach to construct conformationally constrained 2D/3D frameworks with high functional group compatibility and

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• and tested to investigate the details of carbohydrate recognition [1][2][3][4][5][6][7]. It has turned out that carbohydrate–lectin interactions are orchestrated by a multitude of structural parameters. In addition to the configurational characteristics of specific carbohydrate building blocks, homo

• with FimH (Supporting Information File 1, Figures S19–S21). In addition to the π–π interaction of the CRD-bound mannose-projecting antenna of the EE isomer with Tyr48, the complex is stabilized by hydrogen bonds of the scaffold mannoside to Tyr48 and in case of the glucose moiety to Thr51, Ile52, and

• like glycoclusters 1 and 2 are capable of many conformational alternatives and therefore, the control of molecular shape by photoisomerization of azobenzene linkers has its limitations. In addition, water solubility requires improvement. Furthermore, our study, combining synthesis, analysis of

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• and iodine, respectively, were applied to compound 5 to give the chloropropyl and iodopropyl HBC dyes 12 and 13 (Scheme 4). In addition, the HBC alcohol 5 was reacted under basic conditions with methanesulfonyl chloride to give the N-(3-mesyloxypropyl) HBC derivative 14, or with tosyl chloride to give

• counterpart. The tosyloxypropyl HBC analog 15 was also less reactive than its bromo counterpart. Of all the HBC dyes with reactive handles synthesized to date, the highest RNA alkylation yield was obtained with the N-(3-mesyloxypropyl) HBC derivative 14. In addition, the mesyl compound 14 showed significantly

• in 40 µL of water, followed by the addition of 12 µL of buffer (250 mM HEPES, 500 mM KCl, pH 7.0) and 6.0 µL of MgCl2 solution (20 mM). The aptamer was annealed by heat shock at 90 °C for 2 minutes and cooled on ice. Then, 2.0 µL of a ligand stock solution (3.0 mM, in DMSO) was added. The final

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• , 10 min). The crude solid was analyzed by 1H NMR which showed residual pyridine. The crude solid was subsequently dissolved in water (150 mL) and re-precipitated by the addition of EtOH (144 mL) followed by centrifugation (7200 rpm, 5 min) to obtain a white solid. The solid was dried overnight under

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• vs axial). Normally, the pucker with an equatorial carboxyl group is favoured. This pucker is maintained in the difluorinated analogue 97 (Figure 11); in this conformation, in addition to the favourable equatorial placement of the carboxyl group, all of the interactions I–III (Figure 11) are

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• ]. Also, the effects of fluorination on the chiroptical features of [n]helicenes were theoretically predicted [41]. In addition to the manipulation of electronic natures, partial fluorination of PAHs has been recognized to be significant for crystal design and engineering. Thus, molecular packing patterns

• progression. The first phosphorescence vibrational peak was observed at 501 nm for PIC and 514 nm for FUL [48]. In the case of F8-phenacenes, at 77 K, in addition to fluorescence bands, photoluminescence bands assignable to phosphorescence were detected (λPHOS = 518 nm for F8PIC, 528 nm for F8PIC, and 525 nm

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• chiral nickel complexes. In recent years, the Soloshonok working group demonstrated the synthesis of non‑natural amino acids using the corresponding chiral Ni(II) complex [7]. In addition to the high enantiomeric purity of the corresponding products, the scale of the reaction, which extends into the

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• importance of reaction conditions after ZnCl2 addition (Scheme 5). When the reaction mixture was stirred at −30 °C for 1 hour (entry 1 in Scheme 5), the product 19 maintained a high diastereomeric ratio (dr), indicating minimal racemization. However, extending the stirring time or increasing the reaction

• optimization revealed LiOt-Bu and diphenyl phosphate as the optimal metal alkoxide and leaving group, delivering the desired product 32 in high yield and high enantioselectivity at room temperature with only 2 mol % catalyst loading. The scope of this transformation proved to be remarkably broad. In addition

• traditional crotyl addition to acetaldehyde. This methodology represents the first example of highly enantio- and diastereoselective copper-catalyzed allylic substitution that controls vicinal stereogenic centers. DFT calculations revealed that the high enantioselectivity (98:2 er) originates from a face

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• , and afforded trace amounts of 6h together with the corresponding acyclic hemiaminal 10h as the major product. Such an outcome can be attributed to a slower formation of a 6-membered ring [15] from transient N-acyliminium species. Gratifyingly, the addition of KOH (1 equiv) to the electrolysis mixture

• facilitated the cyclization, and the 6-membered heterocycles 6h,i could be obtained in 27% and 18% yield, respectively. In addition to sulfonamides, carbamates such as N-Boc and benzamide are also suitable as nucleophiles for the anodic decarboxylation/cyclization reaction. However, the corresponding 2

• -aminoproline derivatives 6j,k were obtained in considerably lower yields (38%) as compared to those of N-Ts analog 6a. Surprisingly, the addition of KOH (0.5 equiv) to the electrolysis solution has helped to improve yield of N-Boc-protected 2-aminoproline derivative 6j from 38% to 59%. However, the addition of

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• functionalized nature of polypeptides/proteins demands exquisite selectivity to target specific sites on the macromolecule of interest. In addition to the requisite features of the chemical methods outlined above, there are key requirements for synthetic methods used in ADCs, which include high site-selectivity

• particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine

• transformations is a strong electrophile that can react with Tyr, for instance, if such an amino acid is located near the reactive site. In addition, command of the DAR might have some limits, as the distance between the catalyst and the mAbs is not well defined, meaning that the photoredox reaction might not

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• % yield) obtained as a white powder. Its molecular formula C27H31ClO10 was deduced from the HRESIMS spectrum (Figure S2, Supporting Information File 1), which exhibited the sodium adduct at m/z 573.1495 (calcd. for C27H31ClO10Na+: 573.1498) and NMR analysis. In addition to resonances attributed to

• the presence of catalytic amounts of 4-dimethylaminopyridine, 82% yield) was proposed as C32H23Br3O9 based on the molecular ion cluster sodium adducts [M + Na]+ depicted at m/z 810.96, 812.94, 814.92, and 816.90 characteristic for the presence of three bromine atoms [22]. In addition to signals

• Information File 1) which showed the protonated molecular ion peak and the sodium adduct at m/z 325.1281 [M + H]+ (calcd. for C16H21O7+: 325.1282) and 347.1103 (calcd. for C16H20O7Na+: 347.1101), respectively. Its 1HNMR spectrum displayed in addition to signals ascribed to massarilactone D, those of a

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• acidic conditions as key step to construct an aryl-containing quaternary center. The 6/5/6 benzofuran unit was formed through reductive elimination with Zn/AcOH and a spontaneous oxy-Michael addition. This synthesis consists of 8 steps and achieves an overall yield of 13%, making it the shortest known

• construct the aryl and allyl-containing quaternary center, and a simultaneous phenol-initiated oxy-Michael addition to afford the benzofuran unit. This synthesis took 9 steps and achieved an overall yield of 13%. Also in 2024, the Denton group reported another efficient way to access the 6/5/6 benzofuran

• scaffold of simonsol C, utilizing an alkaline dearomatization as the key reaction, followed by a functional-group-selective Wittig reaction and concurrent oxy-Michael addition [6]. A bromophenol acetal was used in the intramolecular alkylative dearomatization, which was first reported by Magnus et al. [8

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• copper(I)-catalyzed reactions (48–71%) [13] and the four-component Ugi reaction [14] yields 48–71% and 27–67%, respectively. In addition, pyroglutamates with isocyanates, which provide exceptionally high yields (97–99%) [15], and dipeptides have been utilized in triflate-activated Mumm’s rearrangement

• second step was attempted as part of a one-pot synthesis of hydantoins by the addition of concentrated hydrochloric acid followed by microwave irradiation of the reaction mixture at 80 °C for 15 min (Scheme 2). Gratifyingly, the acid-induced intra-cyclization of the urea derivative H1a proceeded smoothly

• ][15][16], but reaction times are significantly shorter. In addition, TLC analysis confirmed complete consumption of starting material, which was further confirmed by NMR analysis showing no detectable impurities or unreacted starting material. Variations in yields (34–89%) may be due to differences in

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• decompose into DMS (dimethyl sulfide), which then can act as a nucleophile in several MCRs (Scheme 4) [19][20][21][22]. In this context, DMSO can be used as a source of the methylsulfanyl (-SCH3) group after DMS follows a nucleophilic addition or substitution, allowing one to obtain different types of

• nucleophilic species present in the reaction medium, MMS can act as a methylene source. Under hydrolysis conditions, it can be a source of formaldehyde (Scheme 5a), but with other nucleophiles, after nucleophilic addition, the sulfide group can work as a leaving group, allowing for a sequential domino process

• developed in which the alkene compound has been replaced with other surrogates for electrophilic addition, such as ketones [32][33][34]. In the case of the carbonyl component, it is generally an aromatic aldehyde [30][33][34] and there are not many reports on using formaldehyde in the Povarov reaction. In a