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

• bridged tetrahydrofluorenone derivatives, represented by molecules V and VI, showed significant ERβ binding affinity and high selectivity [15][16][17][18][19]. So far, there are only two routes for accessing bridged tetrahydrofluorenone derivative VI. The first one shown in Scheme 2A includes a Robinson

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

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

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

• reaction carried out in the presence of 5 mol % of NiSO4 gave not only dimer 4, but also the annulation product, compound 3a. Further optimization of the reaction conditions aimed at suppressing the formation of dimer 4 showed that nickel chelates exhibit enhanced selectivity in catalyzing the annulation

• -catalyzed reaction proceeds with low diastereoselectivity. The significant difference in selectivity can be explained by the fact that, in contrast to the Ni(II)-catalyzed reaction depicted in Scheme 3, the copper(I) catalysis involves the coordination by the metal of both reaction partners, and the

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• -bromochromones via a Michael reaction of an amine with an electron-deficient alkene moiety and subsequent photocatalyzed debromination. With this dual catalytic system, a range of structurally diverse enaminone derivatives have been achieved in good yields with total trans selectivity. Mechanistic studies

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• selectivity, and in all cases formation of insertion products of both types, i. e., thioaminals 9 and dithioacetales 10, was observed (see Table 1). Chromatographic separation enabled the isolation of pure compounds, and the more stable dithioacetals 10 formed the more polar fraction. The less polar fraction

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• diaryliodonium salts under photoredox conditions has been proposed for the first time. The suggested procedure allows preparing a broad range of benzamides using both symmetric and unsymmetric diaryliodonium salts under mild conditions. A plausible mechanism for the reaction and the selectivity of aryl transfer

• for unsymmetrical iodonium salts. Therefore, we moved to these to test the selectivity of aryl transfer under the established conditions. Since iodonium salts are prone to repeat the selectivity pattern of nucleophilic substitution in photoredox processes [35][36][37][38][39][40][41], we evaluated

• iodonium salts with common dummy ligands such as 2,4,6-trimethoxyphenyl (TMP) [42][43], sterically hindered 2,4,6-triisopropylphenyl, and mesityl ligands. The highest selectivity was achieved using aryl(2,4,6-trimethoxyphenyl)iodonium triflates 1n–p yielding the desired amides 2ba, 2bo, and 2bp in 25–42

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• demonstrated good product conversion and selectivity without the need to perform the reaction under oxygen, while Cu(OAc)2 was slightly less efficient. When the catalyst loading was reduced to 15 mol %, the reaction yield decreased to approximately 75% for both copper salts. However, reducing the reaction time

• to 6 hours, with a catalyst loading of 20 mol %, resulted in complete conversion and high selectivity, comparable to the results obtained from an overnight reaction. Notably, decreasing the reaction temperature to 60 °C still yielded excellent results with both catalysts after an overnight reaction

• reported in numerous green protocols, offer significant advantages over the use of conventional heating. The goal was to utilise selective, volumetric dielectric heating to save time and energy, enable selective catalysis and generally achieve higher selectivity and yields [53][55][56]. Building on the

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• infants and it has successfully completed a phase III clinical trial [17][18]. Finally, sulphonamide 4 is a lead compound for the treatment of osteoarthritis via MMP-13 (matrix metalloproteinase 13) inhibition which exhibited an excellent selectivity profile and complete inhibition of collagenolysis in

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• transfer (HAT) in photocatalytic reactions. These radicals display exceptional selectivity and efficiency in abstracting hydrogen atoms from C–H, Si–H, B–H, and Ge–H, positioning them as invaluable tools in synthetic chemistry. This review summarizes the latest advancements in the photocatalyzed generation

• /mol (Figure 2a) [28][29][30]. Almost 5 kcal/mol difference between two species could spontaneously undergo a HAT process. That also justifies the selectivity and efficiency of amidyl radical serving as HAT reagent. 2) Recent research indicated a critical correlation between electronic effects and

• a central role in this photocatalytic system. This strategy demonstrated good chemical selectivity for the functionalization of pyridine and alkanes, resulting in 55% to 86% yields of products 38, 39, 40, and 41, respectively. Amidyl radical from N–O bond cleavage In 2022, Alexanian’s group

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• oxidation: The Scholl-type oxidation has also been employed also for azulene-embedded PAHs. where it was used to fuse substituents around the already existing azulene moiety in the direct precursor. However, such reactions often lead to suboptimal results in terms of yield and selectivity. Positions 1 and 3

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• ) [6]. This methodology enabled the selective functionalization of one or two C(sp3)–H bonds adjacent to the nitrile group, leading to the formation of diverse polycycles with high selectivity. Various reaction parameters were systematically examined, including Lewis acids, oxidants, bases, reaction

• selectivity, and high functional group compatibility (65a–f). In 2024, Huang, Liu, and Li’s group introduced a novel approach for the photochemical radical cascade 6-endo cyclization of dienes using α-carbonyl bromides, as illustrated in Scheme 32 [20]. This method is characterized by a visible-light-induced

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• well with the observed reactivities and selectivity. Attempted macrocyclization leading to linear polymers Formyl groups have diverse reactivities and enable facile condensation, dynamic covalent chemistry, and so on. In this work, we tried the synthesis of cyclic oligomers composed of naphthalene

• N2 adsorption and desorption. Molecular design for uniform microporosity and efficient polymerization is a next challenge. Conclusion In this work, we developed formylation on a naphthalene ring in [3.3.3]- and [4.3.3]-type fully π-fused propellanes. High selectivity was achieved for monoformylation

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• the Z-product during the cross-metathesis reactions. Therefore, the synthetic study was initiated by performing cross-metathesis reactions between both (E,E)- and (Z,E)-134 with various alkenes to investigate the Z- or E-selectivity of the reaction. Fortunately, Iqbal observed that all cross

• -metathesis reactions in the study exhibited high E-selectivity. As a result, the reaction of (Z,E)-134 with olefin 135 provided the desired product 136 in 56% yield, with a (Z,E)/(Z,Z) ratio of 4:1 (Scheme 21). Compound 136 was subsequently protected as a TBS ether, 137 [35]. The aldehyde counterpart 147 for

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• compound selectivity was made using the human embryonic kidney cell line HEK293, according to previously reported protocols [16][17]. The results are shown in Table 1, including IC50 values for the reference compounds puromycin, chloroquine, pyrimethamine, and dihydroartemisinin. Compounds 2–9 and 15 did

• limited activity against Pf 3D7 resulted in low selectivity indices, as indicated in Table 1. Compounds 3 and 13–15 demonstrated some inhibition of HEK293 at the highest concentrated tested, but did not display sigmoidal dose-dependent kinetics, thus accurate IC50 values were unable to be determined

• . Meaningful selectivity indices for these compounds could, therefore, likewise not be calculated. Hence, the mean % growth inhibition (duplicate, n = 1) at the top concentration is indicated in Table 1. Conclusion A modified approach for amine substitution of 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• high selectivity. The present review is centered on the use of cyclodextrins, natural and biocompatible oligosaccharides that form upon microbial fermentation of starch. The method is environmentally safe because it resorts to natural compounds, posing as a promising alternative to the use of cyanides

• such as sodium sulfite. As a disadvantage, the step of gold reduction causes co-precipitation of all other metals that are present in solution, which has raised the need for the use of selective precipitation methods. One of the strategies to address this selectivity precipitation issue is the use of β

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• kinetically controlled diastereofacial selectivity. The resulting diastereomers are separable by chromatography. 1H NMR was used to assign the configuration of the 2 diastereomers [53][54][55]. Carbon C2 is R-configured, as ᴅ-2-aminoadipic acid (1) was employed as the starting material. The minor diastereomer

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

• -branched (L/B) selectivity of >20:1. The reaction involves the formation of palladium hydride (Pd–H) 270 as the key species followed by alkyne and CO insertion reactions via 271 and 272 (Scheme 68A) [116]. On the one hand, Jia and co-workers (2021) utilized environmentally benign water as the hydrogen

• -Markovnikov selectivity catalyzed by Au(III) in the presence of dimethylaminopyridine N-oxide (DMAPO) as oxidant. The reaction proceeds via Au–allenylidene species 307 (Scheme 73) [124]. Various cinnamic esters and amides with natural product-based alkoxy groups 301–304 and sulfoximines 305 and 306, a

• cinnamamides 13, 77, 99, and 371 in good yields via the active palladium–hydride species 372 (Scheme 81A) [137]. The Z-to-E-selectivity could be effectively tuned by changing the solvent and temperature from CH3CN to DMF and rt to 80 °C, respectively. Similarly, Wang and co-workers (2023) employed Pd to

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• , which attacks the pendant olefin to form an aziridinium cation (Scheme 2). A sulfonate counter-anion then opens this aziridinium ring in an exo-selective, SN2 reaction. We were successful in scaling the reaction from 0.3 mmol to 11.5 mmol (38-fold increase) without any erosion in yield or selectivity

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• literatures focusing on key regulatory factors for product divergent formation, in which controlling chemical selectivity primarily relies on ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates. To gain a deeper understanding of the mechanisms underlying

• reaction activity and selectivity differentiation, the review provides a systematic analysis of the mechanisms of critical steps through specific case studies. It is hoped that the controllable/divergent synthesis concept will spark the interest of practitioners and aficionados to delve deeper into the

• control The precise regulation of product selectivity represents a fundamental challenge in transition-metal-catalyzed organic transformations, with significant implications for complex molecule synthesis. In this context, ligand-modulated divergent catalysis has emerged as a paradigm-shifting strategy

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

• selectivity for heptanedioate (C72−) was attributed to cooperative hydrogen bonding, anion–π interactions, and a size-matching effect, as supported by DFT optimizations. Keywords: anion–π interactions; anion recognition; hydrogen bonding; dicarboxylates; ultracycles; Introduction Macrocycles containing more

• anticipated to exhibit high association efficiency and selectivity for large guests, driven by cooperative effects of their convergent macrocyclic elements. Dicarboxylates are crucial species in biological system and chemistry [20]. Examples such as malonate, succinate, and glutarate play key roles in

• interactions, the host undergoes conformational adjustments: the distance between the two submacrocycles increases, and the glycol chains adopt extended conformations compared to the structure shown in Figure 1. These results suggest that the experimentally observed strong binding capability and selectivity of

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• and making new receptors, thereby saving considerable time. However, the selectivity of ion separation achieved through the dual-host strategy may not match that of ion-pair receptors, possibly due to less defined interactions between the receptor-complexed anions and cations. Early studies employing

• , the extraction efficiency follows the order of PO43− > CO32− > SO42− > NO3−, consistent with the order of negative charges as well as the anions’ hydration energies (Table 1) [49][50]. This anti-Hofmeister selectivity of phosphate over other studied oxyanions is normally seen in liquid–liquid and

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• by the regio- and stereoselective allylation with p-toluenesulfonyl cyanide. The proposed methodology is efficient for accessing acyclic β,γ-unsaturated nitriles with α-all-carbon quaternary centers and achieves yields up to 99% and excellent regio- and E-selectivity. The reaction proceeds under mild

• , we synthesized new and versatile functionalized acyclic nitriles that include all-carbon quaternary centers with high selectivity (Scheme 1c). Compared to previous methodologies, our approach enables the efficient generation of tertiary nitrile products with a broader substrate scope, highlighting

• efficiently constructed α-all-carbon quaternary centers on β,γ-unsaturated nitriles with excellent >98% regioselectivity and >98% (E)-selectivity. 1,1-Disubstituted allenes bearing silyl ether- and benzyl ether-tethered propyl groups were successfully converted into the desired nitriles 3a–c in yields ranging

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

• that controls reaction selectivity by adjusting voltage or current [13]. Simple synthetic systems in electrochemical methods are limited to electrodes, cells, electrolytes, and power supplies. Today, in addition to the above, light, metallic, and organic catalysts are also used to increase the

• resistance, and maintain ion balance (e.g., LiClO4, n-Bu4NBF4), and active electrolytes, which participate directly in redox reactions, acting as oxidizing or reducing agents (e.g., H2SO4, Et4NOH). Choosing the proper electrolyte affects reaction efficiency, selectivity, and overall performance. Electrodes

• -phosphorylated indole was obtained with high selectivity when n-Bu4NClO4 was used as the electrolyte. Additionally, under certain conditions that reduced the reaction yield, the C3-phosphorylated product was also observed. Similar to previous heteroaromatic coupling reactions with phosphine oxides [53][54], this

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• used, although often with limited success. We believe that the electrophilic warheads presented here offer an excellent balance between reactivity and selectivity for labeling of nucleic acids, and therefore, may also stimulate new designs for RNA targeting and RNA drugging. Experimental General

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• target binding will incur little entropic cost) and high selectivity (since off-target interactions will be minimised) [1]. There are several methods by which the conformations of small molecules can be controlled, but in this review we will focus upon one particular method, which is the installation of

• motif has been exploited in the design of bioactive molecules [22][23] such as the histone deacetylase (HDAC) inhibitors 6 and 7 (Figure 2). The presence of the 1,2-difluoro moiety in 6 leads to greater potency and selectivity for certain HDAC isoforms, attributable to the higher polarity of the

• including protein kinase A (PKA). Fluorination was investigated as a strategy for altering the conformation of the central seven-membered nitrogen heterocycle, and hence possibly improving the selectivity for PKCε. A variety of fluorination patterns were investigated (100–103, Figure 11), which were found