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

• -UV system [column 2.1 × 50 mm, 1.7 μm, C18 Acquity UPLC BEH (Waters), solvent A: H2O + 0.1% formic acid; solvent B: ACN + 0.1% formic acid, gradient: 5% B for 0.5 min, increasing to 100% B in 19.5 min, maintaining 100% B for 5 min, RF = 0.6 mL/min, UV–vis detection 200–600 nm]. NMR spectra were

• ), solvent A: H2O + 0.1% formic acid; solvent B: acetonitrile (ACN) + 0.1% formic acid, gradient: 5% B for 0.5 min, increasing to 100% B in 20 min, maintaining isocratic conditions at 100% B for 10 min, flow = 0.6 mL/min, UV–vis detection 190–600 nm]. Preparative HPLC was achieved at room temperature on an

• Agilent 1100 series preparative HPLC system [ChemStation software (Rev. B.04.03 SP1); binary pump system; column: Kinetex 5u RP C18, dimensions 250 × 21.20 mm; mobile phase: ACN + 0.05% trifluoroacetic acid (TFA) and water + 0.05% TFA; flow rate: 20 mL/min; diode array UV detector; 226 fraction collector

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

• dearomatization offers considerable versatility. Not only can it be employed under basic dearomatization conditions, but it is also effective under Lewis acid conditions. Combined with a reductive elimination using Zn/AcOH, the benzofuran skeleton can be easily synthesized. This dual applicability of the new

• 14 was performed next and the desired iodide was isolated and, to our delight, the cleavage of the MOM group occurred concomitantly, affording compound 15 in 75% yield. This reaction is likely triggered by the in situ-generated acid. As in our previously reported synthesis, a Zn/AcOH reductive

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

• Discussion As the first step of Urech hydantoin synthesis involved the N-carbamylation of amino acids, we carried out the microwave-assisted synthesis of urea derivatives in water, utilizing ʟ-phenylaniline as the representative amino acid. The optimal conditions for the N-carbamylation of ʟ-phenylaniline

• 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

• amino acid. The hydantoins were found to be optically active (except for H2d), suggesting that enantiomeric information was preserved during the reaction (see Supporting Information File 1). Hydantoin yields (34–89%) are generally comparable to previously reported methods [7][8][9][10][11][12][13][14

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

• , several efforts have been made to improve the chemoselectivity of the oxidation step. Among the most relevant examples, o-iodoxybenzoic acid (IBX) has been used in Ugi and Passerini reactions to oxidize the suitable alcohol to the desired aldehyde [13]. Alternatively, catalytic amounts of a ternary system

• consequently, different catalytic strategies to afford the electrophilic addition on the final cyclization step. Finally, other examples show the synthesis of 3-aryl and alkyl quinoline-3-carboxylate derivatives under acid catalysis for the activation of DMSO via the Pummerer reaction (Scheme 10). In these

• was carried out via copper catalysis or iodine–acid catalysis. Interestingly, when aliphatic amines are employed (R3 = n-Pr, n-Bu, product 8) only the N atoms are incorporated in the structure of the final product, probably because the high temperature favors the elimination of the alkyl group. The

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• target product was not obtained (Table 1, entries 3–5). Apparently, the presence of acid reagent is necessary for implementation of considered recyclization. In this regard we tried to perform the process under study using phenylhydrazine in salt form. Indeed, reflux of furanone 1a with the corresponding

• elaborated above for the preparation of enamines 4. Interaction of starting compound 1a with hydrazine was performed using acetic acid as a solvent at reflux for 8 h. As a result, the appropriate pyrazolone 10a, unsubstituted at both nitrogen atoms, was obtained with 73% yield (Scheme 5b). Based on the

• established by X-ray analysis. The proposed mechanism of the considered processes is outlined at Scheme 8. Initially, the free nitrogen nucleophile is reversibly generated from the corresponding hydrochloride or acetate. Next, acid-catalyzed addition of the amine component to the carbon atom of the aroyl

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• peptides [4][5]. Tryptophan also serves as a substrate to produce hormones such as serotonin or melatonin [6][7]. Due to the biological relevance of tryptophan synthetic receptors for this amino acid are highly sought after [8]. From a biological perspective it is especially desirable to achieve selective

• binding of tryptophan in water [9]. However, the development of selective amino acid receptors in aqueous environments is challenging since it requires a combination of hydrophobic and polar interactions for binding [10][11][12]. As a result, the number of reported selective receptors for tryptophan in

• aqueous media is limited (Figure 1a–c) [13][14][15][16][17][18]. In particular, receptors which bind tryptophan residues in peptides are rare [19][20]. Recently, we developed a glucose-based naphtho crown ether 1 (Figure 1d) which binds amino acid methyl esters with aromatic side chains chemoselectively

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• starting materials to study the vinylogous functionalization with alkyl trifluoropyruvates. The synthesis of compounds 3 was accomplished by the reaction of cyclic ketones 1 and 5-aminopyrazoles 2 in the presence of acetic acid (Scheme 1) [30][31]. Cyclohexenones 1a–c provided the corresponding products

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• ] to obtain free acid 11. Exchange of the Boc protecting group of dimethylaniline 8 to an acryloyl substituent and subsequent saponification furnished dimethylamine building block 13. For the macrocycle assembly, especially the ring closure, we decided on two different routes. While the cryptophycin

• macrolactamisation [21]. The syntheses of required unit A [28], C [29][30], and D [31] building blocks were accomplished as described previously. tert-Butyl-protected leucic acid 14 and Fmoc-β-aminopivalic acid (15) were connected by Steglich esterification (Scheme 2) and after cleavage of the tert-butyl ester group

• , HOAt, N,N-dimethylformamide 0 °C for 2 h and at rt for 20 min, 11%; f) Grubbs II catalyst, CH2Cl2, reflux, 3 h, 84%; g) TFA, H2O, CH2Cl2, 0 °C to rt, 5 h, 91%. EDC·HCl = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; DMAP = 4-(dimethylamino)pyridine; TFA = trifluoroacetic acid; HOAt = 1

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• , dried over 4 Å molecular sieves); quinine hemisulfate salt monohydrate (Fluka); sulfuric acid (EMD Chemicals); diethyl ether anhydrous (EMD Chemicals, ACS grade); chloroform-d (CDCl3, Cambridge Isotope Labs, 99.8%); hexafluorobenzene (C6F6, Oakwood Products); deionized distilled water (purified with a

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• (R)-citronellic acid [18], methyl (S)-3-hydroxy-2-methylpropanoate, (S)-2-methyl-1-butanol [19], (R)-2,3-O-isopropylideneglyceraldehyde [20], (R)- and (S)-citronellol [21], (R)-4-methyl-δ-valerolactone [22], porcine pancreatic lipase (PPL)-catalyzed acetylation of racemic citronellol [23], and Evan′s

• enolate of diethyl malonate yielded (S)-2-(hex-5-en-2-yl)malonate ((S)-6), and realized a stereospecific inversion of chiral secondary tosylate (R)-5 [30][31]. The geminal ester (S)-6 was next treated with NaOH in methanol to afford (S)-2-(hex-5-en-2-yl)malonic acid ((S)-7) in 96% yield [32]. Then

• , geminal acid (S)-7 was decarboxylated with DMSO to yield chiral acid (S)-8 [33], followed by TiCl4-catalyzed reduction with ammonia-borane to obtain the chiral alkenyl alcohol (S)-9 [34]. The final tosylation with p-tosyl chloride provided (S)-3-methylhept-6-en-1-yl 4-methylbenzenesulfonate ((S)-10) [29

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• the chlorination reactions on the synthetic path to Cl2B and Me2B, chlorine gas was generated by reacting MnO₂ with HCl and then passed through a stirred suspension of the pyrazolinone. In the case of Me4B, trichloroisocyanuric acid (TCICA) was used as the chlorinating agent as a safer alternative to

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• benzylboronic acid gave the corresponding N-acetyl diazocine 17 (45%, Table 4). Interestingly, this reaction only took place if brominated N-acetyl diazocine 2 was used as starting material although iodoaryl compounds are in general more reactive [25]. The reaction of halogenated N-acetyl diazocines 2 and 3

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

• . Using diphenylamine as a more electron-rich amine resulted in the formation of diphenylamino-substituted N-acetyl diazocine 20 in a significantly lower yield of 25% starting from the bromide 2 and 47% starting from the iodo precursor 3 (Table 5). Deprotection of carbamate 19 with trifluoroacetic acid

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• mild reduction with methanolic sodium borohydride. Upon purification by reversed-phase chromatography using aqueous hydrobromic acid as eluent (0.5% in H2O), a considerable fraction of the alcohols was already converted to the desired bromides 4c,d. Only in the case of 4b, no deoxygenative bromination

• was observed, and the alcohol intermediate was isolated in pure form. In both cases, quantitative bromination was achieved by heating the compounds in concentrated aqueous hydrobromic acid, which after evaporation afforded the pure compounds 4b–d. To generate iodide 4e, alcohol 11 was isolated and

• by displacement of the mesyl group to give a six-membered cyclic carbamate, a reactivity that has been described earlier [34]. Thus, care was taken to quickly isolate compound 14 and use it immediately in the next step. Deblocking of the secondary amine by treatment with trifluoroacetic acid afforded

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• ] using 20 mol % of catalyst A and 20 mol % of p-nitrobenzoic acid (PNBA) as co-catalyst in different solvents at room temperature. The results obtained are summarized in Scheme 3 and Table 1. The progress of the reaction was monitored using thin-layer chromatography (TLC) and 1H NMR analysis of the

• entry 2 versus entry 6 in Table 2). Furthermore, we studied the effect of using an organic acid as the co-catalyst for forming the enamine intermediate from 1 and for the retro-Michael reaction. We observed that benzoic acid (BA) as a co-catalyst provides a lower er than that achieved with PNBA as a co

• a one dm path length, and concentration was given in grams per 100 mL. TLC analysis was performed on glass-backed plates coated with silica gel 60 and an F254 indicator and visualized by either UV irradiation or staining with phosphomolybdic acid solution. Flash chromatography uses silica gel (230

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• -[1,1'-biphenyl]-2-amines 3 with sodium nitrite and an acid under aqueous conditions. Recently, Wencel-Delord and co-workers disclosed an improved protocol toward diazonium intermediates 2 under non-aqueous conditions (t-BuONO and MsOH in acetonitrile) [4]. Nevertheless, the improved method still

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• insufficiently studied furo[2,3-f]isoindole derivatives. Ugi adducts formed from (E)-3-(furan-2-yl)acrylaldehyde, maleic acid monoanilide, isonitrile, and an amine spontaneously underwent the IMDAV reaction with a high level of stereoselectivity, leading to single pairs of enantiomers of 4,4a,5,6,7,7a-hexahydro

• construction [27][28]. For instance, the intramolecular Diels–Alder reactions of vinylarenes (IMDAV) strategy [29][30] has been used to synthesize annulated isoindoles, including thieno[2,3-f]isoindoles [31][32] and furo[2,3-f]isoindoles [33][34], from thienyl- or furylallylamines and unsaturated acid

• the Ugi reaction with a maleic acid to form adducts containing both, diene and dienophilic fragments. It was found that aldehyde 1a reacted with amines 2, isonitriles 3, and maleic acid monoanilide (4a) to form an adduct that spontaneously underwent a [4 + 2] cycloaddition giving furoisoindoles 5a–h

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• typically not possible for imine [314] or metal-coordination cages [156][202][365]. Further, the robust amide cages could withstand harsh conditions such as ester hydrolysis, allowing access to the key acid-functionalized cages [38] that mimic aspartyl proteases and glycoside hydrolases. Otte has employed

• there to be wide-ranging potential across low-symmetry cavity research [205][208][309][366][370][371][372][373][374] if new and more explicit emergent geometric rules can be codified and exploited [39]. We were also able to statistically access a cage with a single internal carboxylic acid group and

• more than 104 compared to the background rate (298 K, CDCl3) (Figure 9B) [41]. Here, the strongly preorganized pair of carboxylic acids split duties: one covalently activates an acyl group while the other provides bifunctional acid/base activation. Together, they bind the transition state

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• product on HPLC even for the reaction of diethylene glycolamine and 1. Capping the free hydroxy group with a methyl group improved the separation on HPLC marginally. However, incorporating a clickable propargyl group greatly benefited separation. Similar to the alcohol, amino-PEG5-acid also reacted with 1

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• . performed glycosylations under solvent-free conditions with poorly reactive disarmed per-O-acetylated (15) and per-O-benzoylated (18) glycosyl donors on being activated in air aided by catalytic amounts of a mild promoter, methanesulphonic acid (Scheme 3) [92]. The ester group was capable of conjugating

• . Levulinoyl protection: Levulinic acid (Lev, 27) as protecting group which can be cleaved using hydrazine hydrate in AcOH, also yields highly selective 1,2-trans glycosides [95][96] and was implemented as a substitute for acetyl or benzoyl protection [97][98]. van Boom et al. also showed the use of a masked

• demonstrated that the use of triflimide (Tf2NH) in solvents like CH2Cl2, acetonitrile or toluene at −78 °C yielded exclusively the 1,2-trans stereoselective glycoside product 105 (protocol A, Scheme 18), while the use of triflic acid (TfOH) in ether as the solvent at ambient temperature conditions (protocol B

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• Comprehensive Cancer Center at University of Alabama at Birmingham, Department of Medicine, Section of Hematology/Oncology, Heersink School of Medicine, Birmingham, AL 35233, USA 10.3762/bjoc.21.26 Abstract The acid-catalyzed reaction of benzo[e(g)] derivatives of 2,3,3-trimethylindolenines with o-chloranil

• is to obtain heterocyclic indole compounds conjugated with a 1,3-tropolone moiety. The variability of the products of acid-catalyzed reactions in the series of 2,3,3-trimethylindolenine with 1,2-benzoquinone derivatives depends on the nature of the substituents in the 1,2-benzoquinone. Thus, the

• 2-(indolin-2-yl)-1,3-tropolones [5]. Unlike the cross-aldol reaction of o-chloranil with methyl ketones [13][14][15], which is always accompanied by the removal of one of the chlorine atoms from the seven-membered ring, the acid-catalyzed reaction between methylene-active heterocyclic compounds and

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -c]chromene-3-carboxylates 5a,b with a yield of 84–85% were obtained under the same conditions as a result of the interaction of bromonitroacrylates 1a,b with 4-hydroxy-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5(6H)-dione (2b) (ratio acrylate/CH-acid/AcOK = 1:1:1.5, room temperature, 1 h) (Scheme 5

• case of 2e) or alcohol (in the case of 2f,g) solution for 1–3 h (ratio of acrylate/CH-acid/AcOK = 1:1:1.5) with a yield of 43–64% (Scheme 7). The structures of the obtained condensed furans 3–7 were characterized by a set of physicochemical methods, including X-ray diffraction analysis. Analysis of the

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• 10.3762/bjoc.21.23 Abstract During the course of our studies on the secondary metabolism of rare, hitherto untapped Thai insect-associated fungi, the ethyl acetate (EtOAc) extract derived from solid-state cultivation of Samsoniella aurantia on rice afforded one previously undescribed tetramic acid

• anticancer properties [6]. With concerns about biofilm formation and resistance escalating in the medical field, entomopathogenic fungi have emerged as a promising source of novel bioactive compounds [5]. Our recent exploration of B. neobassiana highlighted this growing interest, affording one tetramic acid

• spectrum to two sp3 carbon atoms at δC 67.8 (C-2') and 72.6 (C-3'), respectively. These results suggested that compound 1 possesses a tetramic acid moiety similar to prototenellin D (Figure 1), a precursor in the biosynthesis of tenellin [10], a 2-pyridone derivative purified from the entomopathogenic

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• unsaturated ring structure derived from squaric acid [47], has attracted attention due to its ability to promote single-electron transfer [48]. These compounds exhibit significant NIR fluorescence, making them valuable in applications such as biomolecule probing. Additionally, squaraine derivatives are well

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• shift (NICS) calculations and anisotropy of the current induced density (ACID) plots, as they evidenced the presence of a perimetral diatropic global ring current upon oxidation. Keywords: ACID; aromaticity; force constants; NICS; spectroscopy; Introduction Since the discovery of conjugated polymers

• ] reported a stable heptacene dication in concentrated sulfuric acid, a stability attributed to the intermolecular Coulomb repulsion between the charged molecules, which prevents the dimerization of the acene. This exciting finding suggests possible modes of kinetic stabilization of oxidized species of π

• . In this case, the CBDs act as stoppers for whole innermost electron delocalization Anisotropy of the current induced density (ACID) The NICS analysis of the precedent paragraph is therefore consistent with the existence of an emergent global diatropic ring current in m-12+ along the entire molecular

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• [4][5][6] and polymerization processes of unstable methylidene adducts [7][8][9], instead of the desired formation of a monocrotonic product. Therefore, heating [6][10][11][12][13][14] or Lewis acid activation [15][16][17][18] have often been used in the literature for successful multicomponent

• various CH acid derivatives and conjugated dienes (cyclopentadiene, 1,3-cyclohexadiene, 2,3-dimethylbutadiene and isoprene), leading to [4 + 2]-cycloaddition adducts (Scheme 1). It should be noted that in previous works describing three-component reactions of carbonyl compounds, conjugated dienes and

• formaldehyde (generated from paraformaldehyde upon heating), an adduct of a methylidene derivative of a CH acid dienophile was detected in some cases only in reference [15] (when carrying out the reaction in a sealed tube in the presence of copper(II) acetate). However, in most reactions only the hetero-Diels