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

• crystal lattice and are often reversible, requiring either high-energy light or heat for initiation [6][7][8]. Notably, topochemical polymerizations align with the principles of green chemistry, as they are solvent-free and do not involve toxic reagents [9]. The highly ordered and uniform nature of

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy 10.3762/bjoc.21.33 Abstract Photomechanochemistry, i.e., the merger of light energy and mechanical forces, is emerging as a new trend in organic synthesis, enabling unique reactivities of fleeting excited states under solvent

• rearrangements. Most organic molecules are colorless and, in fact, do not absorb visible light: highly energetic UV irradiation is typically needed. A milder approach is offered by photocatalytic approaches. Here, a photocatalyst is added to the reaction mixture to convert light energy into chemical potential to

• transform molecules. Intriguingly, photocatalysts typically absorb harmless visible light and can be chosen ad hoc to trigger the desired chemistry. Indeed, the photocatalyst–substrate interaction can occur via energy transfer [4][5][6][7][8], single-electron transfer [9][10][11][12], or hydrogen-atom

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

• yields. The studied tandem Ugi and intramolecular Diels–Alder reactions allow high substituent variation in the named isoindoles. Keywords: 1,3-butadienylfuran; furo[2,3-f]isoindole; intramolecular Diels–Alder reaction; isoindole; one-pot; Ugi reaction; vinylfuran; Introduction Energy-saving and

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

• therefore can be subjected to automated and high-throughput crystallization studies and, with Szczypiński, Slater, Cooper and co-workers, we were able to isolate all five calculated lowest-energy conformers of cage 1 in the solid state (see crystal cavity heights marked under conformers in Figure 9A) [40

• free energy transition barrier can be framed in terms of contributions from polarization and organization by the catalyst/system. Typical catalysis modes using macrocycle cavities performing (non-specific) hydrophobic substrate binding. (A) Macrocycles that confine two reagents close together to alter

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• a Kohn–Sham molecular orbital analysis together with an energy decomposition analysis (Figure S1 in Supporting Information File 1). To form the broken bonds, both fragments have two unpaired electrons (at their triplet state). The interaction between both fragments amounts to −227.9 kcal mol−1

• -pyrazoline (13.0 kcal mol−1 higher in energy). Also in this case, the five-membered rings are clearly confirmed to be non-aromatic (Figure 4). Conclusion In this work, we have quantum chemically analyzed a series of o-carborane-fused pyrazoles that have been recently synthesized, and whose fusion was

• , the energy decomposition analysis has been performed at the ZORA-BLYP-D3(BJ)/TZ2P level of theory with AMS software [81][82][83][84]. Series o-carborane-fused pyrazoles under analysis. Bond lengths (in Å) of systems under analysis (top row) and reference systems (second and third rows) from the fusion

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

• ], cosmetics, and detergents. Carbohydrates are the most abundant and versatile renewable sources of energy on earth. However, extraction of naturally occurring complex glycans from natural sources is a laborious and cumbersome task. Moreover, the isolated samples provide a low-yield heterogenous mixture of

• pathway. The benchmark for the SN1 spectrum of the mechanistic continuum has been elaborately illustrated and supported by Codee et al. by mapping full ensemble of conformations that the glycosyl oxocarbenium ions can adopt by a complete conformational energy landscape (CEL) study in a quantitative manner

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

• (Scheme 2). The structures of tautomeric forms of 7a, 7b, 8a, 8b and their energy characteristics were calculated by PBE0/6-311+G(d,p) method in the gas phase and polar solvent (DMSO) (Table 1, Figure 1 and Supporting Information File 3). According to the obtained data, the (NH) isomers of 7 and 8 are

• studied compounds. The difference in the energy characteristics of the (NH) and (OH) tautomeric forms of compounds 7a, 7b, 8a, and 8b in the polar solvent and the gas phase is small (2.0–3.8 kcal/mol), and probably the nature of the solvent can influence the shift of the equilibrium towards one of the

• energies with zero-point energy correction (Etot + ZPE, a.u.) and relative energies (ΔE, kcal/mol) of (NH) and (OH) isomers of compounds 7 and 8 calculated by the PBE0/6-311+G(d,p) method in the gas phase (gas) and DMSO solution (sol). Absorption and fluorescence spectral data of compounds 7a,b and 8a,b in

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

• furan-3-carboxylates 6c,d. It was shown that the increased number of conjugated bonds in their molecules leads to a decrease in the energy of the singlet–singlet π→π* transition and the possibility of exhibiting luminescence of the molecules under study. According to the luminescence excitation spectral

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

• on forces and step size. The IEFPCM solvent model [33] was used to simulate the solvent effects of methanol and frequency calculations were used to determine the conformers as minima. Conformers 4.5 kcal/mol above the lowest energy conformer and double conformers were discarded. Time-dependent DFT

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

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• driving chemical transformations under mild and efficient conditions. The use of red and near-infrared light enables deeper penetration into reaction media, reducing the high-energy side reactions commonly triggered by UV or blue light. These features make red-light photocatalysis particularly

• diverse catalyst types and applications. The first section is dedicated to metal-based photocatalysts. Complexes involving metals such as osmium and ruthenium, have dominated red-light photoredox catalysis because of their ability to absorb low-energy photons and sustain redox cycles via stable excited

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

• attracted a growing interest in recent times, both from fundamental and technological reasons [9][10][11]. Antiaromaticity destabilizes the ground state of organic molecules by raising their highest energy occupied molecular orbitals, thus allowing for easy oxidation, doping, and electron-transfer reactions

• peaks, at 0.67 and 1.16 V, were clearly resolved for the linear oligomer 1. For the angular molecule 2, two partially overlapped one-electron peaks appeared at noticeably lower voltages, 0.28 and 0.44 V. This result reflects the higher energy lying HOMO (and easy of oxidation) and stronger overall

• is using energetic parameters unequivocally associated to individual bonds. This is the case of the vibrational force constants [22]. They are defined as the second derivative of the molecular energy, in the minimum energy molecular structure, with respect to the nuclear displacement coordinates

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• -substituted derivatives [21][22]. In comparison to the absorption spectrum of BPP 2, this lowest-energy absorption band of BPP-OiPr 3 was red-shifted by ≈26 nm, which marked the inductive and resonance effects of the electron-donating isopropyloxy group with lone pairs of electrons, raising the HOMO level

• transitions as previously discussed for other BPP derivatives [21][22], the strikingly enhanced molar extinction coefficient observed for the lowest-energy band of BPP-dione 4 (ε = 17000 M−1 cm−1) indicates that the optical transition to the S1 state becomes allowed by this oxidation. BPP 2 and BPP-OiPr 3

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• , various application examples of molecular photoswitches have been reported so far including volumetric 3D printing [12][13], photoresponsive semiconductors [14][15][16][17], photopharmacology [18][19], energy storage materials [20][21][22][23], data storage materials [24], super-resolution microscopy [25

• theory in combination with the 6-31G(d) basis set well reproduces the experimental value of the activation energy for the thermal back reaction of various diarylbenzenes, resulting in the accurate prediction of the half-lifte time [58][63]. Thus, the combination of experiments and theoretical

• compounds N3, N4, and I1–I4. The activation enthalpy (ΔH‡) and activation entropy (ΔS‡) in the thermal reaction were determined from the intercept and slope. Using these values, the experimental activation free energy (ΔG‡(exp)), the k value, and the half-life (t1/2) at 298 K were calculated and the results

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• Goals (SDGs), wherein the 7th goal focuses on ensuring access to affordable, renewable and clean energy [1]. Moreover, the European Union has committed to ambitious environmental targets as part of the European Green Deal [2]. Advancements in C1 chemistry are pivotal to achieving this equilibrium. As

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• . We expect this information to be useful for the rational application of the CF2H group in drug development and molecular design. Previous quantum mechanical calculations revealed that the CF2H···O binding energy (ΔE) ranges from 1.0 kcal/mol to 5.5 kcal/mol [14][15][18][21]. In addition, as measured

• constructs. Although many of the CF2H HB donors studied here can promote relatively strong hydrogen bonding interactions with n-Bu3PO, even the strongest CF2H HB donor (3b) is still 30 times weaker than phenol (10), corresponding to about a 2 kcal/mol reduction in binding energy at 25 °C. These results

• , with other easily accessible parameters. We first calculated the Gibbs free energy of formation (ΔGcalc) of the HB complexes of HB donors with trimethylphosphine oxide (Me3PO), which models n-Bu3PO as a hydrogen bond acceptor, and compared these values with experimental data. We realized that such an

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

• remains a significant challenge owing to the high energy barrier required for oxidative addition and facile β-hydride elimination [12]. The development of radical approaches facilitated by transition-metal catalysis has provided a promising solution to overcome the limitations of conventional coupling

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• organic chemistry owing to their high bond dissociation energy compared to other aromatic C–X (X = Cl, Br, I) bonds [1][2][3][4][5][6][7]. This activation is essential for the late-stage functionalization of stable C–F bonds in complex molecules with reactive functional groups, providing an orthogonal

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

• -catalyzed reaction of indoles 210 with 2-nitrosonaphthalenes 211 was conducted in 2020 (Scheme 63) [93]. In combination with catalyst hydrogen bonding, the nitroso group was identified as a suitable partner for the nucleophilic substitution by possessing a sufficiently low LUMO energy value. Based on the

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• Technological University, Singapore 639798, Republic of Singapore Institute for Functional Intelligent Materials, National University of Singapore, 4 Science Drive 2, Singapore 117544, Republic of Singapore Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science Technology

• energy consumption and reduced use of hazardous materials, contributing to more sustainable chemical processes. Integrating ML algorithms to simultaneously optimize multiple parameters such as yield, purity, and cost within a closed-loop represents a significant advancement in process design. Furthermore

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

• dibenzotropone moieties capable of flapping with small energy barriers. This is supported by the 1H NMR spectrum of compound 1 (Supporting Information File 1, Figure S11), which presents only four different signals due to rapid conformational shifts in solution. Additional evidence of the small energy barrier

• in 3, which consume the energy of the excited state. Figure 4 shows the UV–vis absorption spectrum of 3 in cyclohexane with the absorption edge at 561 nm and its emission spectrum with a peak at 580 nm. In the test windows of cyclic voltammetry (Supporting Information File 1, Figure S1), 3 exhibits

• one reversible oxidation wave and one quasi-reversible oxidation wave with half-wave potentials of 0.40 V and 0.88 V, respectively, versus ferrocenium/ferrocene (Fc+/Fc). The HOMO energy level is estimated from the first oxidation peak to be −5.5 eV [28], which is consistent with the DFT-calculated

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• * transitions associated with the conjugated system, while the band at around 340 nm is attributed to intramolecular charge transfer processes. The low-energy absorption bands of 7-t-Bu (λmax = 345 nm, Table 2) and 7-Cz-2 (λmax = 342 nm) are slightly redshifted compared to 7-H (λmax = 338 nm), and larger

• redshifts are observed for 7-Ph-1 (λmax = 354 nm) and 7-Ph-2 (λmax = 366 nm). In contrast to 7-H, 7-Br (λmax = 327 nm) and 7-Cz-1 (λmax = 316 nm) show a blueshift. With a stronger electron-donating ability than 7-Cz-1, 7-Cz-2 shows a lower energy level for the absorption band stemming from intramolecular

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

• spectra. Their LUMO electron density maps distribute across to the side arm for F1 (−1.88 eV; −1.78 eV for PH1) and to the other triphenylene core for the dimer G11 (−1.78 eV). The π-conjugation of excited states results in a difference of their HOMO and LUMO energy levels: the fluorine dimer G11

• possesses higher HOMO and LUMO energy levels than that of the monomer F1, with a smaller HOMO–LUMO energy gap (3.92 eV for F1 versus 4.11 eV for PH1). The DFT results thus agree pretty well with the fluorescence spectra in solution: G66 shows a fluorescence peak at 470–500 nm, while F6 has peaks located

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• nitrogen atom which is prone to interacting with hydrogen-bond donors or Brønsted acids decreasing the LUMO energy of the diene. This review article aims to give an overview of the non-covalent organocatalyzed cyclization reactions involving α,β-unsaturated imines. Although most of the cyclization

• organocatalyst acts as a Lewis base forming an enamine which raises the HOMO energy of the dienophile, while the thiourea moiety acts as a Lewis acid, lowering the LUMO level of the diene (Scheme 1). A confined transition state is formed providing a high enantiocontrol of the reaction. In 2016, Shi and co

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

• encouraged to further explore these computationally. For both pathways, a potential energy surface (PES) was used to generate an ‘initial guess’ for stationary and saddle point geometries (see also section 4.1 in Supporting Information File 1). The PES scan strongly indicated that the SN2 mechanistic

• proposal was operative, owing to its lower-energy barrier; however, the saddle point geometries identified at this low level of theory were not close enough to the true transition state geometries to meet convergence criteria. Thus, using the guidance of the PES scans, A, XB-2, and B were subjected to the

• was found at a relative energy of 10.1 kcal/mol, where the C–I–C bond angle is 178° with C–I bond lengths of 2.2 Å (I–CH2CF3) and 2.9 Å. The reaction coordinate diagram for path 1 showed a near barrierless equilibrium between halogen bond adducts XB-1 and XB-2, where XB-2 has a C–I–C bond angle of 86

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• conducted at a concentration of 10 μM, with donepezil serving as a positive control. To measure their impact on cellular tau oligomerization, the fluorescence resonance energy transfer (FRET) signal intensity was quantified in a cellular tau FRET assay at the same 10 μM concentration, using MK-886, a known