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

• employed an I2/DMSO-facilitated C–C bond-scission strategy of styrenes, followed by C–N bond formation and subsequent [4 + 2] annulation. Jiang and co-workers developed a method for synthesizing 4-substituted quinolines using vinyl azides as dual synthons, facilitating both the C–C and C–N bond cleavage

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

• , such as tacrine. Therefore, this vesicle system may be suitable for the controlled release of Alzheimer's disease drugs. Extensive research has been conducted on MSN carriers fitted with supramolecular nano valves. Yang and co-workers [121] designed an enzyme-responsive supramolecular nanovalve

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

• added dropwise at 0 °C. The reaction was then stirred for 2 h as the temperature rose from 0 °C to room temperature. The solution was then concentrated in vacuo to yield an oily residue that was co-evaporated with diethyl ether (3 × 10 mL) under vacuum to produce the desired compound 1 as a beige

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

• product from co-migrating monosaccharide by-products. To synthesize fully orthogonally protected 1,1'-linked diglucosamines, the influence of specific combinations of protecting groups on the nucleophilicity of the lactol acceptor and the reactivity of the glycosyl donor was taken into consideration. To

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

• Industrial & Energy Engineering Group Huanghe Construction Co., Ltd., 7 Yandong Xinlu, Lixia District, Jinan 250000, P. R. China China Construction Industrial & Energy Engineering Group Co., Ltd., Nanjing 210023, P. R. China 10.3762/bjoc.21.132 Abstract Flow chemistry technology has demonstrated significant

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

• reaction type and the chirality type of resulting products. Perspective Isocyanide-based transformations Palladium-catalyzed isocyanide insertion reactions In 2018, Luo, Zhu, and co-workers developed a palladium-catalyzed enantioselective reaction between ferrocene-derived vinyl isocyanides 1 and aryl

• ) and aryl iodide 6a as the reactants, diastereomeric products 9a and 9b, each containing two distinct stereogenic axes (C–C and C–N), were obtained in 93% and 89% ee, respectively. Very recently, Luo and co-workers implemented an efficient palladium-catalyzed atroposelective C(sp2)–H imidoylative

• for Pd-catalyzed isocyanide insertion reactions, organocatalytic isocyanide-based multicomponent reactions have been explored for the synthesis of axially chiral compounds. In 2024, Yang and co-workers reported a catalytic asymmetric version of the Groebke–Blackburn–Bienaymé reaction [32][33][34

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

• catalysis, and this arsenal of catalysts is constantly expanding. In this thematic issue, the Dell’Amico group describes the development of a new class of organic donor–acceptor photocatalysts that show promising activity for several transformations [18]. Additionally, Hoffmann and co-workers contributed a

• of alkenylboronic esters using energy transfer catalysis [26]. Gualandi and co-workers leveraged a combination of photoredox and HAT catalysis to realize the intramolecular nucleophilic amidation of alkenes with β-lactams [27]. Further, Luridiana and colleagues developed a method for the alkylation

• catalysis that does not require exogenous photocatalysts has emerged as a new paradigm in photochemical synthesis [33]. Here, a transition metal complex plays a dual role by harnessing photon energy to facilitate bond-breaking and bond-forming events. For example, Sipos and co-workers demonstrate in this

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

• University, Beijing, 100871, China 10.3762/bjoc.21.127 Abstract A formal synthesis of product VI with tetrahydroflurenone structure as selective estrogen receptor modulator has been realized. The Rh-catalyzed [3 + 2 + 1] reaction of yne-vinylcyclopropanes and CO (20 mmol scale, in 87% yield) for building

• annulation to construct the C ring (cyclohexenone ring), and an intramolecular SN2 reaction to build the D ring (five-membered ring) [15][16][17][18]. In 2013, Wallace and co-workers disclosed the second route for this molecule (Scheme 2B) [19], in which the five-membered ring B was formed by utilizing

• group in compound 10. Compound 10 can be realized by introducing an ester group in 9, which is the [3 + 2 + 1] cycloadduct from 8 and CO using a Rh catalyst. The [3 + 2 + 1] substrate of yne-vinylcyclopropane (yne-VCP) 8 can be synthesized by Wittig reaction from cyclopropyl aldehyde 7, in which the

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

• Cope rearrangements [20]. More recently, Alabugin and co-workers reported that the gold(I)-catalyzed propargyl rearrangement depicted in Scheme 1b also follows a concerted oxonia Claisen pathway (via an aromatic TS) rather than through a higher barrier 6-endo-dig cyclization [21], which provides

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

• trials for post-resection hepatocellular carcinoma [26]. Interestingly, Ferro and co-workers revised the structure of PI-88 to I and II in 2017 via successful separation of oligosaccharide phosphate fractions by preparative ion-exchange chromatography (Scheme 1A) [27]. Besides the major components α(1→3

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• : Experimental and computational details, synthesis and characterization of compounds, additional spectroscopic results, and theoretical calculations. Acknowledgements The authors acknowledge Dr. Tatsuo Nakagawa, UNISOKU Co., Ltd., for nanosecond transient absorption measurements Funding This work was supported

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

• = 6.3 Hz, 1H, CH), 2.73–2.02 (m, 4H, CH2); 13C NMR (75 MHz, CDCl3, TMS) δ 200.3 (CO), 101.5 (CH), 73.1 (CH), 67.6 (CH2), 31.1 (CH2), 29.9 (CH2). The NMR data correspond to the published results. Methyl 4-methoxyvalerate and ethyl 4-ethoxyvalerate were prepared using the published method [47]. 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

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

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

• ]. Thiocarbonyl S-methanides (thiocarbonyl ylides) 1, which were first reported in the 1980s by R. Huisgen and co-workers contributed to a substantial extension of mechanistic interpretations of cycloaddition reactions and to rapid development of methods applied not only for the synthesis of sulfur heterocycles

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• biosynthetic pathway for brassicicenes, which share the same carbon skeleton and similar oxidation and unsaturation states as cotylenol and cotylenin A [36]. In a previous study, Oikawa and co-workers reported the identification of brassicicene BGC in Pseudocercospora fijiensis [37]. By heterologous expression

• the homologous gene abnABCDE. As expected, compound 5 was produced at a titer of 8 mg/L (Figure 2c). By co-fermenting with Amberlite XAD-16, an enhanced yield of 30 mg/L was achieved, thus allowing further transformation into other natural products. We next carried out the formal synthesis of

• cotylenin A by Nakada and co-workers [21]. However, installing the C9 hydroxy group requires the use of stoichiometric MoOPH [39], which raises toxicity and safety issues. Therefore, we sought an enzymatic method to selectively oxidize 5 at the C9 position. Dairi and co-workers reported that Orf7 oxidizes

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

• substitution pattern on the regioselectivity and stereoselectivity of the reactions. A Review article by Papis and co-workers discusses various copper(II) triflate-catalyzed multicomponent reaction types [2]. Therein, the synthesis of cyclic and acyclic compounds, as well as three-component and four-component

• by Son and co-workers illustrates recent advancements in the use of dioxazolones in synthetic transformations with copper salts [4]. The authors remark that these catalytic systems, which employ dioxazolones as electrophilic amide sources, were applied for the preparation of diverse amidated products

• . In their contribution, Son et al. focus on transformations via the formation of copper nitrenoids, particularly amidations via oxidative insertion to N–O bonds and reductive elimination, and a small number of other reactions. The final Review by Cho, Lee, and co-workers is useful for the scientific

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

• devoted to benzoxazoles. When applied to benzoxazole, the reaction is catalysed by transition metals such as Ag(I) [20], Mn(II) [21], Fe(III) [22][23], Co [24], Ni(II) [25] and Fe(III) [26]. However, the use of Cu(II) has increased thanks to its high tolerance towards several functional groups, high

• being applied when reacting amides to achieve their decarbonylation. In 2014, Cao et al. [47] reported the amination of benzoxazole with a secondary amine either in air or an O2 atmosphere, lowering the catalyst amount and the reaction temperature. In 2020, a study by De Vos and co-workers [48] focused

• to identify mild conditions for the Cu-catalysed aerobic C–H amination in absence of acid, base or co-catalyst additives. As described in Table 1, we explored the effects of different solvents and copper species, and preliminary reactions were conducted with Cu(II) salts, with reference to reaction

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• helical architectures, have attracted considerable attention due to their intrinsic chirality and tunable optoelectronic properties. Among them, nitrogen-doped helicenes (azahelicenes) and their heteroatom-co-doped counterparts – such as B/N-, O/N-, S/N-, and Se/N-doped helicenes – have emerged as highly

• emitters. Boron–nitrogen co-doping strategies, in particular, have facilitated the development of materials with ultra-narrowband emissions, near-unity photoluminescence quantum yields, and electroluminescence dissymmetry factors (|gEL|) exceeding 10−3. Likewise, heteroatom co-doping with oxygen, sulfur

• applications in chiral optoelectronics. Several comprehensive reviews have examined specific classes of these molecules. Crassous and co-workers provided a detailed overview of heterohelicenes up to 2019, focusing on their structural diversity and functional applications [11]. Nowak-Król and colleagues

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• tautomer, which means that the switching would not be clean. According to relative energies and relative Gibb’s free energies, collected in Table 1, compound 1 should co-exist as a three component (E, KE and KK) tautomeric mixture in both toluene and acetonitrile. If the relative energies are taken into

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

• loadings were necessary for ortho-substituted phenyls. Control experiments and DFT calculations revealed that the oxetane ring is formed before the tetrahydrofuran in the domino process. In 2023, Shigehisa and co-workers published a new cycloisomerisation strategy for the construction of oxetane rings from

• oxidation of the metal centre turns the cobalt into an excellent leaving group, allowing for an intramolecular displacement reaction that affords the oxetane ring and regenerates the Co(II) catalyst. In 2023, Silvi et al. described a versatile and practical methodology that couples Williamson etherification

• vinylsulphonium triflates 28 which combine the features of a radical acceptor (in a Giese-type addition) and a leaving group. The use of ketyl radicals for oxetane synthesis was also investigated by Schindler and co-workers and a year later the group published a methodology that utilises a similar Giese addition

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

• ], TPH-graphene (Figure 2b) [23], PHH-graphene [24] and ψ-graphene [25]. Notably, fragments phagraphene and TPH-graphene have already been synthesized via on-surface chemistry and characterized using low-temperature scanning probe microscopy with CO-functionalized tips [23]. These non-alternant carbon

• synthesis of π-extended azulene was the non-benzenoid isomer of pyrene published by Ward and co-workers (Scheme 1) [31]. Cyclohept[bc]acenaphthylene (2) was obtained from a partially saturated precursor 1 via dehydrogenation using palladium on carbon. However, the reaction carried out at 300 °C gave 2 as a

• . Dehydrogenation played a pivotal role as a key step also in the synthesis of larger π-scaffolds. For example, Murata and co-workers reported the synthesis of an azulene containing isomer of benzo[a]pyrene 9 (Scheme 2) [33]. Reduction of ketone 7 using LiAlH4 resulted in alcohol 8 which was subsequently

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

• , People’s Republic of China Zhejiang Lvgu Biopharmaceutical Co., Ltd., No.16 Bailian Road, Nanmingshan Street, Lishui City 323000, Zhejiang Province, China 10.3762/bjoc.21.98 Abstract The field of radical-mediated functionalization of N-arylacrylamides has experienced considerable advancements in recent

• methoxy (-OMe) and halogens (-F, -Cl, -Br), as well as electron-withdrawing functionalities like trifluoromethyl (-CF₃) and ester groups (-CO₂Me). However, highly electron-deficient substrates, such as those bearing cyano (-CN) or nitro (-NO₂) groups, did not react. Additionally, the study explored

• employed as a redox catalyst, Na2CO3 as a base, and n-Bu4NBF4 as the electrolyte, all participating in an undivided electrolytic cell with a reticulated vitreous carbon (RVC) anode and a platinum (Pt) cathode at a constant current of 10 mA, in a co-solvent mixture of MeOH/THF 2:1 for 3 hours to deliver the

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• molecules that increase the directing strength of a directing group towards a specific site. While this paper was in review, Oshiya and co-workers published an ML model that classifies reactants as having ortho-, meta-, para- or non-directing functionalities for Pd-catalysed directing group-assisted C–H

Correction: Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha,
• Lakshminarayana Satham and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93

• reaction; tetrahydrochromenones; Lakshminarayana Satham is acknowledged as additional co-author of our original publication. It was subsequently determined that Lakshminarayana Satham made significant contributions to the published research. The Funding section is updated as follows: DN thanks UGC India

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

• a marine or hypersaline environment natural products library to identify potent drugs, a putatively novel metabolite co-produced with borrelidin was discovered, expanding the potential for new borrelidin derivatives. This led to the formation of the so-called “borrelidin family” (Table 1), with

• approach for constructing Morken’s C2–C12 fragment In 2019, Uguen and co-workers introduced a strategy to assemble Morken’s C2–C12 intermediate 20 [41]. Their approach utilized iterative base-catalyzed condensation of sulfone compounds with epoxides. As illustrated in Scheme 1, the monoalcohol 20 was

• alternative route was also proposed for synthesizing 21 from compound 30, which was derived from ent-29. Notably, epoxides 23a and 23b were obtained via Sharpless epoxidation of (E)-2-butenol. Uguen and co-workers began their synthesis by reducing Roche esters 29 and ent-29 to their respective primary