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

• fashion, substituted indolopyrimidone derivatives 7a–e were obtained within 3 h in 31–90% total yield (2 steps) upon heating with formamide (Scheme 5). Next, we characterized certain physicochemical properties of the newly synthesized compounds. The absorbance and emission spectra of 5–7 were obtained

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• secondary amines via an N-acyl nitrene intermediate [77]. Amidines, found in biologically active compounds, have been widely investigated in medicinal chemistry due to their potent antiviral, antibacterial, anticancer, and other therapeutic properties [78][79][80][81]. As shown in Scheme 4, dioxazolones

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• of noncovalent interactions that work independently from each other [5][6][7][8]. Generating such motifs with orthogonal propensity is appealing not only for the construction of supramolecular polymers with the ability to modulate their structure and properties in multiple ways through adjustment of

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

• behavior or reactivity properties. The ambiguity related to the role of Cu(OTf)2 is particularly relevant for cycloaddition reactions, where it is even more difficult to justify the activation of the copper species as a Lewis acid or metal catalyst [12][13][14]. The reaction mechanism involved can be ionic

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

• becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• broadening their potential applications in drug delivery and nanotechnology. Our findings shed light on the unique capabilities of polysarcosine-based polymers, paving the way for further exploration and harnessing of their distinctive properties in biomedical research. Keywords: biodegradable; poly(benzyl

• properties. Moreover, these materials offer versatility in their synthesis, allowing for the incorporation of various building blocks to tailor the polymers to desired specifications. Additionally, they lend themselves well to the synthesis of block copolymers, further expanding their potential applications

• properties are crucial, particularly its permeability. Excessive permeability allows water molecules – and potentially larger molecules – to traverse the membrane without exerting adequate force, undermining the transformation process [20][21]. Lastly, membrane stiffness plays a role; the stiffness of the

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ; phenethylamine; Introduction The phenethylamine scaffold represents a recurring motif among natural and synthetic drug molecules. The latter are mainly constituted by a varied class of substituted phenylethylamines exhibiting psychoactive properties, and typically employed for medical and recreational use [1][2

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

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

• the 1880s, Schwarz described triply periodic minimal surfaces, which serve as the topological foundation for what are now known as Mackay crystals. Despite predictions that carbon schwarzites would have intriguing properties for various potential applications [4][5], they have not yet been

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

• HRMS spectrometry were in full agreement with the expected structures, and single-crystal X-ray diffraction analysis was conducted to confirm the structure of compound 7-H. Moreover, the photophysical properties of these PhFlOP derivatives were determined by UV–vis absorption and photoluminescence

• studies, revealing that their photophysical behavior can be affected by the different substituents in the donor carbazole group. Keywords: carbazole; D−A−D type; noble-metal-free system; 9‑phenyl-9-phosphafluorene oxide; photophysical properties; Introduction π-Conjugated molecular materials containing

• ]. Compared to the traditional PO-containing moieties, PhFlOP possesses an enhanced rigid structure to reduce the possibility of nonradiative decay processes, which would improve optoelectronic properties [17][27]. Thermally activated delayed fluorescence (TADF) materials and devices have emerged rapidly in

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• focus of extensive research within the past two decades due to their interesting structural features, attractive photophysical properties, and diverse applications [2]. Indeed, fluoranthenes are particularly useful in supramolecular chemistry, organic electronics, and materials science [3] as

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

• tuneability of the optical and electronic properties, which can potentially be exploited for advanced applications in display technologies, photonic devices, sensors, and organic electronics. We recently successfully reported the straightforward synthesis of several mesogens containing four lateral aliphatic

• critical role in the engineering of functional and complex supramolecular assemblies [3][4][5][6][7][8][9][10][11], ranging from rigid crystalline architectures [3][4][5][6][7][8] to soft liquid crystalline materials [9][10][11]. Their unique properties originate from the high electronegativity of the

• fluorine atoms, inserted in the aromatic rings, which considerably modifies the dipole moment of the corresponding fluorinated aromatic rings with respect to their hydrogenated homologs, thus influencing their behavior, binding affinities, and optoelectronic properties. These interactions already represent

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

• moiety in up to 99% yields, up to 93% ee and >20:1 dr (Scheme 5) to be obtained. In general, the steric and electronic properties of the conjugated imines had a slight effect on the enantioselectivities of the reactions. However, the authors pointed out that the azlactones with different substituents at

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• groups (CF3 or CF2H) in organic molecules can modulate their physicochemical (pKa, lipophilicity), structural (additional hydrophobic and hydrogen-bond interactions), and biological properties (metabolic stability, membrane permeability) [14][15]. Alongside the very well-known CF3 group, the CF2H group

• electronic and structural properties of the fluorinated groups (CF3 or CF2H) and the geometric constraints due to its partially unsaturated cycle, which could help in the design of peptidomimetics. To our knowledge, only a few publications report the synthesis of tetrahydropyridazines with a carboxylic acid

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

• antioxidant properties were determined by oxygen radical absorbance capacity assay (ORAC-FL), expressed as Trolox equivalents (TE) and using fluorescein as probe. Additionally, the study investigated the ability of the compounds to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in

• were also remarkable, yielding a value 2-fold higher than melatonin (ORAC = 2.45 TE). Natural polyphenols have shown promising potential in inhibiting β-amyloid aggregation and also antioxidant properties, suggesting their effectiveness in preventing AD. To address this, Lambruschini et al. [36

• antioxidant properties and notable inhibition of Aβ1-42 self-aggregation (65.6% of inhibition). These findings suggest FATH 5a as a potential lead compound for further investigation in AD therapy. In 2016, the same group developed ferulic acid–tacrine–melatonin hybrids (FATMHs) and lipoic acid–tacrine

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• less of an azocorannulene and more a pentaphenylpyrrole, which explains its ease of synthesis and the physical properties [21][22]. The graph with four benzene elements and a CpH core is evident in the commercially available tetrabenzofluorene, TBF (Scheme 3, lower). The parent and the phenyl TBF

• an “azacorannulene”. Working from graph structures based on chemically stable (“group elementary”) nodes is a useful principle in molecular design and chemical synthesis. Such a perspective is important to understand fundamental physical organic molecular properties as well as to predict desirable

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

• 4 [9][10] (Figure 1). Halogenated cyclised structures have also been found to exhibit medicinal and pharmaceutical properties, including antibacterial [11], antibiotic [12], and enzyme inhibition [13] among others. The general mechanism for the HVI-mediated halocyclisation of alkenes proceeds

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• and separation technology [3][4][5][6][7][8]. Conversely, porphyrins are connected via methine (=CH-) bridges, resulting in an 18 π-electron macrocyclic system affording macrocyclic planarity as well as unique photophysical and electrochemical properties (Figure 1b). While corroles share similarities

• that function as hydrogen-bond donors and acceptors. Additionally, the nitrogen atoms in the pyrrole units of the porphyrin structure can also act as Lewis bases, capable of donating electron pairs. These properties enable tetrapyrrolic macrocycles to act as effective binding sites or catalytically

• affect the optical and electronic properties, as well as the reactivity of porphyrins, mainly introducing non-planarity with easier access to the inner pyrrolic –NHs and –N-lone pairs. Additionally, these alterations potentially increase Lewis basicity that further improves interactions with substrates

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• potential in anticancer drug design. However, it should be taken into account that the sulfonyl group can radically change the pharmacokinetic properties of a drug, so the effect it may have on its ADMET properties should be determined in an additional study. Conclusion A novel synthetic strategy has been

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• molecular system. Herein, we present the synthesis of mono-, bis-, and tris-norbornadiene derivatives with alkynylbenzene and alkynylnaphthalene core units, along with studies of their photochemical properties. The target compounds were synthesized by Sonogashira–Hagihara coupling reactions of 2

• ], azobenzenes [16][17][18][19], dihydroazulenes [20][21], or azaborines [22][23]. However, the most prominent feasible MOST system is the [2 + 2] photocycloaddition–cycloreversion cycle between norbornadiene (1a) and quadricyclane (2a), which has several advantageous properties (Scheme 1) [8][14][24]. In

• , such as realized in bis- and tris-norbornadienes 1b–f (Figure 1) [7][12][30][34][35]. In this particular case, derivatives with only one substituent at the norbornadiene double bond exhibited favorable storage properties because of a lower molecular weight, however, their absorption still lies in the

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• structure of a molecule defines its properties and reactivity, and therefore dictates how it interacts with other molecules. Microorganisms need to communicate with each other and the environment, secreting signals of friendship, disdain, and many other sentiments in between. Natural products are the

• properties. Specifically, Qian and co-workers examined 7395 bacterial genomes and identified more than ten thousand potential cationic NRPs. They focused on a few promising candidates after bioinformatic-based dereplication and found two NRPs, brevicidine and laterocidine, that worked in an animal thigh

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• ][15]. A variety of unique rotaxane-based architectures (e.g., mechano-responsive material, polymers exhibiting pump-like motion, and biomimetic sequential reactors) exhibiting conventionally unaddressed unique properties have been developed based on modern synthetic chemistry [16][17][18][19][20][21

• typical ring molecules [31][32][33][34][35]. Meanwhile, the studies on CD-based rotaxane are generally divided into two aspects: (1) the construction of a complicated small-molecule framework and the evaluation of its properties, and (2) the development of a polymer material (e.g., polyrotaxane) with a

• materials and fabricate polymer materials featuring a defined rotaxane structure. In this review, this issue is discussed in three sections: (1) synthesis and structure of CD-based (poly)rotaxanes, (2) structural control of the (poly)rotaxane framework, and (3) properties and applications of rotaxane-based

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• chemistry. This type of chromophores is of particular interest in the fields of organic electronics, photonics, and optoelectronics due to their unique optical and electronic properties [1][2][3][4][5][6][7][8][9][10][11][12][13]. Among heteroaromatic push–pull molecules, stilbazole derivatives

• pyridine as an acceptor. The introduction of additional substituents to stilbazole makes it possible to change the optical properties of this molecular framework within a wide range [16][17][18][19]. This approach has found many applications in the synthesis of compounds that are used in various optical

• , full-color fluorescence of organic molecules is achieved by extending π-conjugated systems or by introducing combinations of donor and acceptor groups, which changes the electronic properties and consequently the emission spectra [35][36][37][38][39][40][41][42][43][44]. This approach is synthetically

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• ready receptor preparation by metal complexation. The reason for the underrepresentation is the competitive nature and excellent ligand properties of oxalate which not only is associated with the aforementioned diseases but also poses a serious hazard for metal-driven self-assemblies because the dianion

• equiv oxalate alone. The competition experiments clearly show that the host favors and binds oxalate selectively over all other guests of this study. Conclusion Oxalate as highly competitive dianion with excellent coordinating and chelating properties was successfully recognized by a charge-neutral self

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• Poznań, Poland 10.3762/bjoc.20.247 Abstract The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation