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

• [53]. In this work, the authors used a stoichiometric amount of Zn(OTf)3 as a Lewis acid catalyst and air as the oxidant for the reaction. Jana and colleagues demonstrated an atom-efficient pseudo-three-component C–H annulation reaction catalyzed by Yb and Cu, which involved nitrosoarenes and styrene

• , the present C–H annulation reaction of aniline (1a) with styrene (2a) was initially carried out in TFE (trifluoroethanol) as solvent in the presence of 25 mol % FeCl3·6H2O as a catalyst and 1.5 equiv of TFA (trifluoroacetic acid) as an additive (Table 1, entry 1). For this reaction, 12% of 2,4

• cleavage as well as inadequate Lewis acid activation of N-methylaniline (1a′), which hinders its further cyclization into the final product 3a′. The reaction, when conducted in the absence of a catalyst, failed to proceed, thereby highlighting the crucial role of catalytic activation in facilitating the

[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

• 1–5e with para-methoxy group in the aromatic ring (Table 1, Supporting Information File 1, part 2). Typically thioformylium methylide is generated from compound I by action of CsF or TBAF [16][23][24]. We also tested other fluorides and trifluoroacetic acid (Supporting Information File 1, part 2

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines

• , condensation of N-sulfonylated 1,2-diphenylethane-1,2-diamines and cyclohexane-1,2-dicarboxylic acid, and the final cyclization with the in situ generated Hendrickson reagent. Keywords: bisimidazoline; cyclohexane; cyclohexane-1,2-dicarboxylic acid; 1,2-diphenylethane-1,2-diamine; Introduction Chiral

• bisimidazoline (PyBim) ligands derived from pyridine-2,6-dicarbonitrile or pyridine-2,6-dicarboxylic acid and vicinal diamines, as analogues of pyridine-linked bisoxazoline (PyBOX) ligands [16][17]. They exhibited excellent performance in metal-catalyzed asymmetric organic reactions. Chiral rigid backbone-linked

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

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

• a hot topic [75]. PAs can be prepared via the Friedel–Crafts condensation, which involves combining 1,4-dimethoxybenzene with paraformaldehyde in the presence of a Lewis acid. The central axis of these aromatic hydrocarbon molecules possesses n fold rotational symmetry [76]. PAs possess highly

• ]arene (WP7) by adding 14 anionic carboxylic acid groups to both sides [102]. They explored the pH-dependent complexation of WP7 with paraquat derivative G1 in water. The host WP7 and guest G1 form a 1:1 pseudorotaxane, with an association constant of (2.96 ± 0.31) × 105 M−1. Furthermore, they leveraged

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• oxidation in methanol in batch electrolysis conditions, providing unsaturated esters S-3d and R-3d, respectively (Scheme 2). The previously used one-reactor two-step conditions were found to be productive for the electrosynthesis of S-3d, requiring the addition of acetic acid for the intermediate spiroketal

• reaction, and we found that acetic acid served well for this purpose (Table 1, entry 4). Using the reaction conditions with acetic acid as additive, the reaction could be performed also in a 0.5 g scale for the synthesis of both ester enantiomers S-3d and R-3d (Table 1, entries 5 and 6). In the absence of

• acetic acid or HFIP the electrochemical oxidation also provided the desired product 3d, although in reduced yield (Table 1, entry 7). An increased amount of acetic acid (1 mL or ≈ 18 equiv) also reduced the yield (Table 1, entry 8). The attempt to use LiOAc as electrolyte instead of LiClO4 was not

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• receptor agonist and potential glucokinase activator, we developed a convenient synthetic route from commercially available indole-3-acetic acid. Treatment of the N-Boc-protected indole-3-acetic acid with N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of DMAP generates the N,N′-Boc

• ]. Herein, we report an alternative synthesis from commercially available indole acetic acid, and demonstrate that the approach can be extended to related compounds. Results and Discussion Previously, malassezione had either been (i) isolated from cultures of M. furfur grown on ʟ-tryptophan as the sole

• nitrogen source followed by thin-layer chromatography and reversed-phase (RP)-HPLC to isolate and purify the compound from a complex mixture of indole alkaloids [11], (ii) prepared by aerobic incubation of indole-3-pyruvic acid at pH 7.4, 37 °C for 24 h followed by isolation and purification using RP-HPLC

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

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• the formation of a borate complex [61]. Diarylborinic acids have also been exploited for stereoselective 1,1'-glycosylations through the formation of a 1-O-monoborinate ester, resulting from the complexation of a 1,2-dihydroxyglycosyl acceptor with a diarylborinic acid derivative. Concurrent

• the orthogonally protected diol acceptor 36, proved to deliver optimal stereoselectivity and the highest yields in the reaction promoted by bistrifluoromethylated tricyclic borinic acid 40, affording β,α-1,1'-linked disaccharides 37 [63] and 39 [62], respectively, in 86% yield (Scheme 4). The nature

• of the 2N-protecting group on GlcN- and GalN-derived lactol acceptors proved crucial for the success of borinic acid-promoted glycosylation, as the 2N-Troc-protected acceptor 41 failed to participate in the reaction. In contrast, the 2N-naphthalenesulfonyl (NapSO₂)-protected glucosamine-derived

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

• development, and (ii) refining existing synthetic processes through process intensification strategies. Nitric acid (HNO3) and its binary systems with sulfuric acid (HNO3/H2SO4) remain the industry-standard nitrating systems, particularly for the nitration of aromatic substrates. Motivated by environmental

• technologies including ultrasonication, microwave irradiation, and microreaction technology into conventional nitration frameworks. Nikseresht et al. developed a novel heterogeneous heteropoly acid catalyst (PMA@MIL-53(Fe)), enabled efficient regioselective nitration of phenols under ultrasonic irradiation

• , achieving 54.98% o- and 45.01% p-nitrophenol yields within 15 minutes [10]. Umrigar et al. demonstrated a microwave-assisted nitration of monochlorobenzene (MCB) for the efficient synthesis of 2,4-dinitrochlorobenzene (2,4-DNCB), achieving reduced reaction time, minimized waste acid, and enhanced yield

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

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

• the foundational work of Kulkarni, Codée, Boons, and other outstanding groups in their studies on zwitterionic polysaccharides [7][8][9][10][11][12]. Pyruvylation of carbohydrate diols is commonly achieved through acetal substitution in the presence of acid during chemical synthesis. In this process

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

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

• absence of an external hydrogen source. The alternative pathway to form a hemiaminal could not include the interaction of an acid with amine or aldehyde, nevertheless, the non-catalytic path had ΔEa = 32.1 kcal/mol (TS2→3'') which meant that hemiaminal definitely emerged faster via the amine protonation

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

• ] involving 6-aryl-2-aminopyridines 27, aldehydes, and isocyanides (Scheme 5a) [35]. By employing chiral phosphoric acid (CPA) C1 as the catalyst, this reaction worked well to afford axially chiral imidazo[1,2-a]pyridines 28 in high-to-excellent yields (up to 99%) and enantioselectivities (up to >99% ee). It

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

• of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular

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

• . Unfortunately, failure was encountered here. This can be expected because the reaction site here is a bridge quaternary center (no such example was reported in literature for this) [31][32][33]. Due to this, we then converted the ester group in 12 into a carboxylic acid group, reaching 13 in 72% yield. Finally

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

• analysis in terms of stabilization energy. In addition, an analysis of the Anisotropy of the induced current density (ACID) plot [24] calculated for 1 (Figure 3B) shows a significant diatropic ring current formally associated with the peripheral model 1b. Another diatropic contribution can be assigned to

• Equation 1. (B) Anisotropy of the current induced density (ACID) diagram of compound 1. (isosurface value: 0.035 a.u.) (C) Bond distances (in Å) for fully optimized structure of 1, computed at the ground state (S0) and at the first singlet excited state (S1, in orange). Results obtained at the B3LYP-D3BJ/6

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

• this perspective article, we shall show the relationship between transition-state aromaticity and reactivity in representative pericyclic reactions. Perspective Lewis acid-catalyzed Diels–Alder cycloadditions It is well-established that catalytic amounts of a Lewis acid (LA) can significantly

• following subchapter) but also to other processes such as aza-Michael additions or processes catalyzed by species able to establish noncovalent interactions with the reactants [52][53][54][55][56][57]. Lewis acid-catalyzed carbonyl–ene reactions Similar to the Diels–Alder cycloaddition reaction, the Alder

• , which is translated into high reaction temperatures that severely limit the scope of the process. Nevertheless, as Diels–Alder cycloadditions, Alder–ene reactions can be efficiently accelerated (i.e., having lower barriers) upon the addition of catalytic amounts of a Lewis acid [62], which again

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

• -containing compounds [1][2][3]. Such reactions can be initiated by electrophilic, nucleophilic or radical reagents, photoirradiation or proceed under acid-, metal-, or photocatalytic conditions. This strategy of azirine ring expansion is applicable to the synthesis of a variety of 4‒9-membered N-heterocycles

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• of polar groups, including phosphoryl acid and amine groups [62]. After several optimizations, the following sequence was adopted to remove all Bn, Bz, and Cbz groups: 1) global hydrogenolysis of Bn and Cbz groups in 12 with Pd(OH)2/C in a mixed solvent (THF/MeOH/AcOH/H2O) and 2) saponification of

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• 060-0812, Japan 10.3762/bjoc.21.120 Abstract pH-Responsive molecular switches and motors are a class of organic molecules whose three-dimensional structure can be changed by acid–base stimuli. To date, pH-responsive molecular switches have been developed using various functional groups, but further

• triggered by protonation and deprotonation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. This class of molecules has the capacity to regulate three-dimensional structures and motions of molecules through simple acid–base stimuli. This provides a high degree of control over their

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• precursors 4a–c were then prepared by the reaction of compounds 3a–c with N-chlorosuccinimide (NCS) in dimethylformamide (DMF). The ester group-containing chloro oxime 4d was obtained by the treatment of glycine ethyl ester hydrochloride with sodium nitrite and hydrochloric acid [25] and used thereafter as

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• Discussion We recently demonstrated that Pd-catalyzed Heck reactions could be performed in CyreneTM [26]. To extend its applicability, we first compared the typical conventional organic media, selected biomass-derived solvents (i.e., levulinic acid and γ-valerolactone-based solvents), and CyreneTM in the

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• -dichloroethane and highlight its potential for temperature sensing applications. Density functional theory calculations were performed to support our findings and to investigate the mechanisms of azobenzene–acid interactions, aiming to guide the design of azobenzene-based temperature sensors in future research

• affect the protonation itself. In this study, we investigate the temperature dependence of azobenzene protonation with the aim of utilizing it in temperature sensing. We focus on steady-state behavior of azobenzene, 4-methoxyazobenzene, and 4,4’-dimethoxyazobenzene in solution. By tuning acid strength

• . We opted for methoxy substitution on one or both benzene rings as the simplest alkoxy substituent. The protonation of azobenzene (1), 4-methoxyazobenzene (2), and 4,4'-dimethoxyazobenzene (3) is schematized in Figure 1A. In the presence of a strong acid, these compounds form an equilibrium of neutral

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• acetylene production, was investigated. The catalyst was obtained by calcination of calcium carbide slag at 600 °C (CS600) and characterized by XRD and FTIR analysis. The transesterification reactions were carried out with primary alcohols, producing fatty acid alkyl esters in 51–99% yields, depending on

• [31][32][33][34], and cosmetic industries [16][17][35][36]. Fatty acid methyl esters (biodiesel) are of particular interest due to their current use as fuel in vehicles and promising applications [37][38][39][40][41][42][43]. The esters are demanded in large amounts according to available methods for

• was calcined at 600 °C before use and the catalyst CS600 was characterized using XRD and FTIR analysis, confirming the presence of CaO as the main phase. The primary alcohols successfully reacted in the transesterification reaction to give the corresponding fatty acid alkyl ester mixtures in yields

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• several-fold higher than that of molecular switches with a single switching unit known. The comparison is made for an AB derivative (4-(phenylazo)benzoic acid) (PABA) and a pyrazole-AB derivative (E-4-((1,3,5-trimethyl-1H-pyrazol-4-yl)diazenyl)benzoic acid) (PyABA) on a graphite surface under similar

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• process of 4,4-dichloro-2-butenoic acid derivatives and bis(pinacolato)diboron is described [10]. The transformations feature excellent chemo-, regio-, and diastereoselectivities, and the resulting products are highly functionalized. Due to this, they were considered as versatile building blocks for the