α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• [40] activities. Furthermore, a quinoxaline-containing commercial drug, caroverine, has been proven effective in the treatment of tinnitus [41]. In addition, in vivo studies in mice and rats with various quinoxalinone derivatives have shown favorable analgesic and anti-inflammatory properties as well

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• combined with state-of-the-art multireference quantum mechanical calculations to understand the photophysical properties and mechanisms of these diazabicyclo[2.2.1]heptenes. The energetically accessible lowest excitations are nNN(σCN) → π* and range from 3.94–3.97 eV. From the >292 trajectories, the

• properties of 1, 3, and 5. We considered the molecular orbitals and electrons most critical for describing the electronic structure of the molecules in the reaction. The CASSCF [87]/ANO-S-VDZP [88] active space for 1 is shown in Figure 1; we considered 8 electrons and 9 orbitals, along with their average

• 0.045. These results show agreement between the electronic nature of the transition of TD-DFT, CASSCF, and CASPT2, showing that the chosen active space can capture the photophysics of the molecules. Table 1 provides the photophysical properties for the optimized ground-state geometry. However

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

• important in pharmaceuticals, catalysts, and advanced materials due to their unique stereogenic scaffolds and associated properties. Consequently, synthetic chemists have been pursuing molecules featuring these forms of non-central chirality, where the stereogenic elements are not localized on a single

• factor considered, without taking into account the electronic, steric and conformational properties. For example, the stereocontrol of the desymmetrization reaction in Scheme 7E [31] would require the catalyst to discern between the two non-reactive ortho-substituents at distant points across the

• . Nonetheless, the stereocontrol connectivity index can provide information on the stereochemical properties of reactions, beyond the existing binary (yes/no) stereochemistry classifications in widely used chemical databases such as CAS SciFinder and Reaxys. This exercise applies not only to existing asymmetric

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

• rearrangements via the 1,2-silyl shift, enabled by the β-cation-stabilizing properties of silyl groups [19][20]. This phenomenon has been successfully employed in 1,3-difunctionalization events in both intermolecular [21] and intramolecular fashion [22] (Scheme 1B). Thus far such propargylsilane rearrangements

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• transition-metal-catalyzed acylations is a notable advantage compared to enzymatic methods. In the case of local desymmetrization, the enantioselectivity of the reaction depends predominantly on the inherent properties of the substrate. Although numerous examples of enantioselective desymmetrization

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

• revealed the formation of isomeric products depending on the substituents on the N atoms. Notably, two intrinsically chiral macrocycles MC1 and MC3 with C1 symmetry were successfully obtained. These macrocycles exhibit exceptional photophysical properties, particularly remarkable high fluorescence quantum

• design novel macrocyclic frameworks with intrinsic asymmetry. Nitrogen (N)-doped macrocycles are of peculiar interest due to their unique optical, electronic and magnetic properties [16][17][18][19]. Among them, aza[1n]metacyclophanes, in which m-phenylene units are linked via N atoms, serves as N

• chiral macrocycles, have been reported [17][25], highlighting a critical gap in the design of chiral macrocycles with tailored electronic landscapes. Herein, we reported the synthesis, characterizations and photophysical properties of inherent chiral N-doped macrocycles (Figure 1b) via regioselective

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• case of MCF7. Additionally, linear sweep voltammetry (LSV) studies on human serum albumin (HSA) were conducted to investigate their alkylating properties. The electrochemical results suggest that these compounds effectively modify albumin, highlighting their potential as reactive anticancer agents

• agent; glycidyl ester; electrochemical evaluation; phosphorus-containing drug; Introduction Phosphorus-containing drugs represent a crucial category of therapeutic agents, extensively utilized in clinical practice due to their diverse pharmacological properties and applications [1][2][3][4]. These

• chemical literature regarding the biological activity (including anticancer properties) of phosphoric esters, reports on biological studies of systems based on the P=O fragment and oxirane skeletons are less common. Nevertheless, systems containing both of the mentioned structural motifs are rarely

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• voltammetry measurements were also carried out in order to evaluate the electrochemical redox properties of the species involved in the process and to provide evidence for the behavior of the monoprotonated and the bisprotonated diimines, 3a and 4a (Scheme 8). The cyclic voltammogram of the starting diimine

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

• catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• may be overwhelming: azobenzene is undoubtedly the most famous due to its easy synthesis and the extensively studied properties. However, there are several photoswitch classes beyond azobenzene with interesting properties that can be tailored to meet one’s needs. In this tutorial review, we aim to

• explain the important terminology and discuss the synthesis, switching mechanisms, and properties of seven interesting photoswitch classes, namely azoheteroarenes, diazocines, indigoid photoswitches, arylhydrazones, diarylethenes, fulgides, and spiropyrans. Keywords: photoswitches; photoswitch properties

• ; synthesis of photoswitches; switching mechanisms; tutorial review; Introduction Photophysical properties and switching mechanism Key learning points Switching mechanisms and the change in properties. Overview of the major classes of photoswitches beyond azobenzenes. Main synthetic pathways for their

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• biocatalysts, as well as enzymatic processes. Among these, molecular oxygen stands out as a greener and more sustainable oxidant due to its natural abundance, low cost, and environmentally friendly properties, making it an appealing option for both academic research and industrial applications. Recently, some

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• were formed, and the transformation rate was extremely low. This outcome may be attributed to the electron-acceptor properties of the oxygen atom, which likely disrupt the cycloaddition process. NMR analysis confirmed that each heterocyclic ring formed products exclusively as a single diastereomer

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

• in pH, light, and enzyme activity, the binding affinity between the guest and host molecules can be altered, thereby achieving controlled drug release and targeted delivery. (2) Drugs are loaded into self-assembled host–guest systems [29][30][31][32]. The chemical structure or properties of the host

• processes. For example, supramolecular self-assembly technology enhances the targeting of chemotherapeutic drugs to tumor tissues, reducing systemic adverse reactions. (3) Macrocyclic aromatic supramolecular nano-valves have a pseudo-rotaxane structure with host–guest coordination and the kinetic properties

• applications. This section will focus on the structural features and applications of CAs and PAs. 1.1 CAs: structure and properties CAs are the third generation of supramolecular hosts [40], succeeding cyclodextrins and crown ethers. They are macrocycles composed of phenolic units condensed with formaldehyde

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• C–N atropisomers and their structural properties for over 25 years [16][17]. As a part of the C–N atropisomeric chemistry, we succeeded in the asymmetric synthesis of mebroqualone (I) and the thione analogue II [18][19]. In the course of this study, it was found that intermolecular association in

• , ought to have different halogen bonding properties, and should be explored as different chemical entities. Meanwhile, there are very few studies on halogen bonding related to molecular chirality such as those shown in Figure 1 [27][28][29][30]. In addition, the studies on the comparison of

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• to modulate properties that enhance the performance of pharmaceuticals and materials. This quantum-chemical study explores the energetic implications of fluorinating cyclopropane, providing insights into molecular characteristics arising from the polar C–F bond. Isodesmic reactions revealed that the

• advanced materials, particularly those whose properties rely on the polarity and spatial arrangement of C–F bonds within a cyclopropane framework. Keywords: cyclopropane; fluorination; polarity; theoretical calculations; Introduction Cyclopropane, the smallest cycloalkane, has a rigid structure that

• polarity, with these effects varying based on the amount, position, and orientation of the fluorine substituents [7][8]. Mondal and colleagues have extensively reviewed additional properties of fluorinated cyclopropanes, including the conformational behavior of substituents attached to a fluorinated

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• , 45141 Essen, Germany 10.3762/bjoc.21.134 Abstract Chiral macrocycles hold significant importance in various scientific fields due to their unique structural and chemical properties. By controlling their size, shape, and substituents, chiral macrocycles offer a platform for designing and synthesizing

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

• syringe pumps. The selection criteria must account for operational pressure thresholds, reagent rheological properties (e.g., viscosity), and required flow regimes. A representative challenge arises when handling high-viscosity nitration agents like the HNO3/H2SO4 binary acid system for which HPLC pumps

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• , and the immunological properties may base on R/S-configuration. However, precisely controlling the formation of R- and S-isomers and identifying the correct conformer can be challenging due to the structural similarities between these two isomers. Researchers have recently developed strategies to

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• pH 0) [19], and usage of an additional amount of base leads to stronger reductive properties. Moreover, the role of the cation could be critical for the thermal stability against disproportionation or aerobic oxidation of hypophosphite [38]; salts with larger cations are also more soluble in organic

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• ; photochemistry; Soon after its first reported synthesis in 1936 [1], [Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine) and its derivatives attracted significant attention due to their photophysical properties [2][3][4]. These complexes can efficiently absorb visible light through a metal-to-ligand charge transfer (MLCT

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• have 75-fold selectivity of ERβ over Erα [12]. Molecules III and IV (Scheme 1A) with an additional pyrazole ring compared to I and II had good pharmacokinetic properties that had overcome the problems of rapid clearance and low oral bioavailability executed by previous molecules [13][14]. A series of

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• properties [10]. Therefore, in this paper, we reexamine the electronic features of these 1-arylbenzo[a]imidazo[5,1,2-cd]indolizine-based FBIs in terms of aromaticity (a relevant feature to analyze the nature of the excited states) and emission properties. The final goal of this research has been to

• contribute to the design of a second generation of bicolor fluorescent indicators for barium tagging in neutrinoless double-beta decay. Results and Discussion First, we analyzed the aromaticity of parent benzo[a]imidazo[5,1,2-cd]indolizine 1 (Scheme 1) in order to get a better understanding of the properties

• + prompted us to compare the photophysical properties of unbound compound 18 in the presence of Ba(ClO4)2. The values corresponding to the adiabatic absorption (S0(optimized) → S1*, adiabatic absorption) and emission (S1(optimized) → S0, fluorescence) are reported in Table 2, together with the differences

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• to the preparation of triazaphospholes and triazaarsoles, π-conjugated species with potential applications in materials science due to their luminescent properties [98]. However, these heavier alkyne analogues are typically kinetically unstable, which limits their use as dipolarophiles. Despite that

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• structures, such as one-handed helical and propeller-shaped structures, can be constructed by folding the π-conjugated system using [2.2]paracyclophane as the chiral crossing unit, leading to circularly polarized luminescence (CPL) properties. Chiral cyclic dimers and trimers were synthesized using planar

• chiral [2.2]paracyclophane-containing enantiopure ribbon-shaped compounds as the chiral monomers. Unicursal π-conjugated systems were folded at the [2.2]paracyclophane units, and exhibited good photoluminescence quantum efficiencies and CPL anisotropy factors. Opposite chiroptical properties were

• ]paracyclophanes via Wurtz-type intramolecular cyclization [3]. [2.2]Paracyclophane has a molecular structure in which two benzene rings are stacked face-to-face with ethylene chains at the para positions. Various studies have been conducted on their reactivities and physical properties derived from their unique

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• ester group. In our case, the demethoxycarbonylative annulation enables the formation of aromatic tricyclic benzo[4,5]thieno[3,2-b]pyrrole system which is encountered in compounds with antitumor activity [21][22] as well as in compounds exhibiting fluorescent properties [22][23]. Since general methods