Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• higher oxidation potential (E1/2 = +1.52 V). This reaction was examined using different solvents, and it was found that toluene and 1,4-dioxane gave low yields (4–5% yield). Under blue LED irradiation, Ir-based PC is photoexcited, and its excited state is reductively quenched by the electron-rich arene

• is reductively quenched by arene 16, producing the corresponding aryl radical cation C and 3CzCIIPN•– (E1/2 red = +1.56 V vs SCE). PC•– then reduces the azolium ion A (E1/2 = −0.81 V vs SCE) to generate the ketyl radical B, thereby closing the photoredox catalysis cycle. 2-Methoxynaphthalene produced

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• , and low toxicity make calixarene derivatives valuable drug candidates against cancer. The aim of the present study was the synthesis and characterization of a calix[4]arene derivative in which known anticancer isothiouronium groups were clustered on a calix[4]arene scaffold bearing long C12 alkyl

• chains at the lower rim. The resulting amphiphilic calix[4]arene derivative 3 spontaneously self-assembled into nanoscale aggregates in aqueous medium, as demonstrated by dynamic light scattering analysis. The cytotoxicity of compound 3 towards cancer cells was assessed using human renal carcinoma cells

• confirmed by comparison with the calix[4]arene precursor (1) lacking these functional units. The selective antiproliferative profile of compound 3 highlights its potential as a lead anticancer agent. Moreover, compound 3 holds promise for further development in combination multidrug therapy due to the

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• other bioactive properties [37][38][39][40][41][42][43][44]. In contrast, examples of 1,5-diaryl-1,2,3-triazoles with quinoline or isoquinoline subunits are lacking [45]. The neighboring proximity of the arene subunits in such 1,5-regioisomers allows for potential intramolecular annulation to form

• impact on yield due to inverting the 1,2,3-triazole connectivity. With the goal of defining the physical and biological properties of these annulated pentacyclic aromatic heterocycles relative to their individual arene components, a “non-annulated” counterpart for each pentacyclic ring system was also

• prepared via base-catalyzed click reaction [53] of aryl azides with commercially available phenylacetylene. Due to the free rotation of the single bonds connecting each arene subunit to the bridging triazole ring, these 1,5-diaryl-1,2,3-triazole compounds can adopt significantly different overall molecular

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• include systems employing CBPQT4+ [43], cucurbit[7]uril [44], tetralactam [45], and pillar[5]arene [46]. Moreover, Qu and co-workers synthesized [2]rotaxanes with a biphenyl and an azobenzene acting as recognition units for an α-cyclodextrin macrocycle, which has two distinct fluorescent bulky groups as

• dendrimer that incorporates about 21 individual azobenzene-based rotaxanes serving as branches distributed within the dendrimer skeleton [50]. The [2]rotaxane consists of a pillar[5]arene macrocycle and an axle featuring a urea and alkyl chain as recognition sites. The azobenzene functioned as one of the

• property, in addition to facilitating their study and isolation, is advantageous for various applications. The first stiff-stilbene-based rotaxane was reported in 2018 [79]. This [1]rotaxane used stiff-stilbene as one of the stoppers, and its photoisomerization produced the translation of a pillar[5]arene

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• , graphene functionalized with β-cyclodextrins [18], a starch-based β-cyclodextrin polymer [19], and pillar[5]arene-based crosslinked polymers have also been investigated as sequestrants for dyes [20]. The Isaacs group has a longstanding interest in the synthesis and mechanism of formation of macrocyclic

• uptake capacity of H2 for methylene blue, it must be substantially lower than that of previously reported pillar[5]arene (51 mg g−1) and calix[4]pyrrole (454 mg g−1) polymers [17][20]. Host G2W1 functions the best as sequestrant for methylene violet achieving an 87% removal efficiency when excess G2W1

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• representative of the stereochemical-determining elementary step. The stereocontrol connectivity indices can be extended to reactions that establish planar chirality (Scheme 5). In the case of metallocenes, the metal is considered to be σ-bonded to the arene ring for convenience. In other words, the centroid

• atom is treated as a pseudo-tetrahedral center, with the metal regarded as one of the substituents. Accordingly, a C–H activation reaction that forms planar chiral ferrocenes [18] is assigned as [30] (Scheme 5A). For cyclophanes, if the bond formation or cleavage is on the stereogenic arene, the

• the other hand, if the bond formation/cleavage is within the macrocycle, the stereochemical differentiation atoms are traced to the stereogenic arene. Therefore, the CALB-mediated esterification to cyclophenes [21] is [53], regardless of the length of the linkage (CH2)n (Scheme 5D). In recent years

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• synthetic potential of iodane-mediated carbofunctionalization under copper catalysis. Keywords: arylation reactions; copper-catalysis; iodanes; propargylsilanes; 1,2-silyl shift; Introduction Highly electrophilic hypervalent iodine(III) reagents are considered as arene electrophilic synthons, making them

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• , including molecular bowls [11][12][13] and medium-sized macrocycles containing a saddle-shaped eight-membered ring [14][15]. In the past decades, despite rapid progress in chiral macrocycles, inherent chirality is largely limited to calix[n]arene derivatives. This underscores a critical opportunity to

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• for interconversion. However, steric repulsion between the C-1 substitutions and the terminal arene moieties in the M-conformational diastereomer resulted in the P-conformational diastereomer being thermodynamically favored. This led to the formation of (P)-helicene products following DDQ-mediated

• enantioselectivity, with an s-factor up to >259 (Scheme 7). Notably, this reaction did not produce the typical arene C–H amination products but instead the dearomative amination products 26, which is believed to be due to the significant steric hindrance surrounding the amination site that impeded the subsequent

• the 1,3-phenyl rings (see 53d) or 1,3-diamino substitution (see 53e) on the calix[4]arene scaffold were also amenable to this method, which yielded a series of structurally diverse novel quinoline-containing inherently chiral calix[4]arenes. Moreover, by using CPA 4 as the optimal catalyst, the

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• molecules and high-selectivity binding in drug-controlled release. Many calix/pillar[n]arene hosts are soluble in water, particularly macrocycles that are modified with carboxyl and phosphate groups. Moreover, their amphiphilic modification ability allows easy self-assembly into functional materials like

• environment, which significantly enhances the density of π-electrons. This structural feature makes pillar[n]arenes particularly effective at encapsulating guest molecules that are either electron-deficient or neutral. For example, pillar[5]arene (PA5) has a strong binding affinity for neutral guest molecules

• drug design and therapeutic strategies. Notably, PA derivatives also exhibit specificity in recognizing important molecules in biological processes, such as acetylcholine [80], amino acids [81], doxorubicin (DOX) [82] and antibiotics [83], etc. Among the many derivatives, water-soluble pillar[5]arene

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• reactions up to 2021, and summarized the characteristics of the main organic nitrating reagents discussed in their work [6]. Yang et al. developed 5-methyl-1,3-dinitro-1H-pyrazoleas a controllable nitronium ion source for mild, selective (hetero)arene nitration. This method achieves condition-controlled

• selective mono- or di-nitration and facilitates late-stage C–H nitration of biorelevant molecules, with DFT/mechanistic studies revealing synergistic 'nitro effect' and 'methyl effect' underlying the reactivity [7]. Jia et al. developed dinitro-5,5-dimethylhydantoin (DNDMH) as an efficient arene nitration

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• chiral INT-C, which, after imine-enamine tautomerization, led to the formation of final product 28. α-Acidic isocyanide-based transformations De novo arene formation In 2019, Zhu and co-workers developed the first example of catalytic enantioselective Yamamoto–de Meijere pyrrole synthesis [36][37

• ] between alkynyl ketones 33 and isocyanoacetates (Scheme 6) [38]. The success of this study not only adds a new entry to the de novo arene formation strategy [39][40] but also initiates the application of isocyanoacetates in constructing axial chirality. With Ag2O and quinine-derived amino-phosphine ligand

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

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

• . Optimization studies identified the tetraphenyl-substituted PyBox ligand L1 as particularly effective in controlling the stereochemistry of the polycyclization, yielding high enantioselectivity for most substrates. As illustrated in Scheme 5, tertiary enamides with a tethered electron-rich arene could undergo

• attack of the electron-rich arene on the acyliminium ion occurs from the Si-face. This stereochemical outcome is attributed to the steric discrepancy of the phenyl or tert-butyl group and the hydroxy group. The resulting tricyclic products could be further elaborated by elimination or amide reduction to

• diastereo- and enantioselectivities. The substituent on the enamide could be varied from aryl to tert-butyl groups, though the terminating aryl group still necessitates an electron-rich arene. As was found in their previous work, the steric hindrance of the phenyl or tert-butyl group was supposed to be

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

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

• , we report the design of ultracycles constructed from functional tetraoxacalix[2]arene[2]triazine submacrocycles. These submacrocycles feature hydroxy groups as hydrogen-bonding (HB) donors on the lower rim, which, in combination with electron-deficient triazines, create cooperative HB and anion–π

• ) solution of the compound at 4 °C, enabling structural analysis of the ultracycle. As illustrated in Figure 1, the backbone of B4aH adopts a Z-like shape with a flexible conformation. The two oxacalix[2]arene[2]triazine subcavities are positioned along the short axis in a staggered face-to-face arrangement

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

• arylphosphonates via carbon–phosphorus bond formation. In 2021, Xu et al. [52] reported an electrochemical process for synthesizing arylphosphonates through the hetero-coupling reaction of CH of arenes with a trialkyl phosphite. They have prepared 45 arene phosphonates with good to excellent yields and reported

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

• versions. Recent advances using hexameric resorcin[4]arene-based capsules [122][123][124] (Figure 4B and C), notably by Tiefenbacher [105][125][126][127][128][129][130][131][132][133], have demonstrated substrate-controlled selectivities that vary from the bulk phase due to the stabilization of cations in

• instance, the window[1]resorcin[3]arene capsule type [135] demonstrates that the symmetry and properties of traditional symmetric capsules can be modulated, although precise control over the assembly remains difficult. Finally, we must mention the recently reported cavitand capsules of Gibb, who has

• ) Self-assembling capsules can perform hydrophobic catalysis [116][117]. (B) Resorcin[4]arene building block. (C) Hexameric resorcin[4]arene-based capsules [122] include structural water. The cavity can stabilize cations (substrates or transition states) and perform catalysis using dual activation of a

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• elimination, produces C–H alkynylated arene 10, which then forms the final product 3 through intramolecular cyclization. Finally, the Cu(I) complex 9 produced via reductive elimination is reoxidized at the anode to regenerate the Cu(II) complex 4, completing the catalytic cycle. Yao and Shi developed the

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

• involves a Friedel–Crafts alkylation of the arene followed by hydroamination (Scheme 6) [5]. The mechanism plausibly starts with the in situ formation of triflic acid from Cu(OTf)2 which leads to protonation of the oxygen atom of the alcohol with generation of the activated allyl alcohol. This latter gives

• the allyl carbenium ion VI through the loss of a molecule of water, then undergoes a Friedel–Crafts alkylation by attack of the aromatic partner. The outcome of the reaction proceeds through a Markovnikov protonation of the allylated arene VII by triflic acid, which generates the carbocation

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• process was inspired by the biocatalytic synthesis of aromatic polyketides by polyketide synthase from poly β-carbonyl substrates. Pyrrolidine-based organocatalyst C4 was able to promote a twofold atroposelective arene-forming 6-enolendo aldol condensation (Scheme 4). Sparr also realized a central-to

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• , expanding its π-skeleton through the Barton–Kellogg and Scholl reactions led to the successful synthesis of a curved polycyclic arene containing three heptagons and two pentagons. Keywords: carbon schwarzites; polycyclic arenes; Scholl reaction; seven-membered carbocycle; Yamamoto coupling; Introduction

• synthesis of 1 using a Ni-mediated Yamamoto coupling reaction and the simultaneous crystallization of its two different conformers from the same solution. Expanding the π-skeleton of 1 through a Barton–Kellogg reaction followed by a subsequent Scholl reaction resulted in a new polycyclic arene (3 in Figure

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• -67034 Strasbourg, France 10.3762/bjoc.20.270 Abstract The high potential of non-covalent arene–fluoroarene intermolecular interactions in the design of liquid crystals lies in their ability to strongly promote self-assembly, improve the order and stability of the supramolecular mesophases, and enable

• derivatives and the antiparallel stacking mode into columnar structures stabilized by arene–perfluoroarene intermolecular interactions were confirmed by the single-crystal structure of the alkoxy-free side chain analog, i.e., 1,2,4-trifluoro-3-(perfluorophenyl)triphenylene (F). UV–vis absorption and

• red-shift of the emission peak. Keywords: arene–perfluoroarene interaction; decafluorobiphenyl; fluorinated triphenylene; fluoroarene nucleophilic substitution; organolithium; Introduction Non-covalent arene–fluoroarene intermolecular interactions [1][2] are drawing increasing attention due to their

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• % yield, and comparable yields were observed for the p-tolyl and p-chlorophenyl derivatives 3n and 3o. A slight increase in yield was found with the p-anisyl derivative (3p, 61% yield), whereas the yield decreased when the arene was appended with an electron-withdrawing CF3 group (3q, 45% yield). Though

• generated using an isodensity surface of 0.001 a.u. [50]. This showed two sigma holes of different potentials, with the stronger (0.21 e) residing opposite the arene, and the slightly weaker (0.20 e) hole residing opposite the trifluoroethyl motif (Figure 3, left). These sigma-hole potentials are consistent

• arene moieties. These observations confirmed the LUMO as an appropriate lobe for nucleophilic attack via the SN2 pathway (path 2), and confirmed the LUMO+1 as an appropriate lobe for substitution via reductive elimination (path 1). As such, neither mechanism could be immediately discarded, and we were

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• via electrochemical oxidation of 4-iodotoluene at the anode, in a 5:6 HF:amine mixture to cyclise a range of phenolic ethers 33. Tolerance for substituents on both the aromatic ring and the alkene were shown, although the electronic requirements were quite narrow for reaction success. As the arene