Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• linker are highlighted in red. Sequences for RNA hairpins and PNA ligands used for binding studies. Major-groove view of hydrogen-bonding interactions in the (A) Db1*U–A triplet, (B) Db2*U–A triplet, (C) Db2*C–G triplet, and (D) Db3*U–A triplet. Carbon, hydrogen, oxygen, and nitrogen are labelled in

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• Atropisomers are not only prevalent in biologically active natural products and pharmaceuticals, but they have also garnered increasing attention for their effectiveness as ligands and catalysts in the field of catalytic asymmetric synthesis. Asymmetric catalysis serves as a key strategy for the

• compounds can participate in asymmetric synthesis reactions and construct chiral molecules with specific stereoconfiguration, which is particularly critical for drug synthesis [9]. In the field of organic catalysis, chiral organic selenium-containing compounds can be used as chiral ligands or catalysts to

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• catalysis affords the dual advantages of introducing stereochemical discrimination on both the radical and the trap via chiral ligands. Early research on parameters governing stereoselectivity in radical reactions was achieved with the help of radicals or radical traps appended with chiral auxiliaries. The

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• substrate class. Through mechanistic-guided modulation of catalysts, solvents, ligands, and angle strain, this approach achieves unprecedented reaction pathway control while demonstrating superior temporal and step efficiency compared to conventional methods. The work establishes a sustainable framework for

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

• heterocyclic scaffolds, which established a versatile platform for synthesizing structurally diverse indoline frameworks. Ligand-controlled cyclization of 1,n-enynes The core function of catalyst ligands lies in their ability to precisely modulate catalyst performance through electronic and steric effects. The

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• affinity of ligands towards the CLK3 kinase. It is based on the lysine 241 which is present only in CLK3, while the three others (CLK1, 2, and 4) have apolar leucine in this position. Thus, by grafting an extra benzoic acid on a molecule previously established as having low activity on CLK3 (DB18), we have

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• regioselectivity issues, multistep procedures, and limited applicability to tetra-ortho-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C–N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and

• the presence of water, highlighting its robustness. Keywords: azo compounds; cross-coupling; domino catalysis; palladium; phosphine ligands; Introduction Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety

• (allyl)2 in DME with strong base (Cs2CO3) favors C–N-bond coupling, which may yield products resulting from arylation at either the terminal or internal nitrogen atoms. The selectivity can be influenced by the steric hindrance of the phosphine ligands and/or the substrates. Once N,N-diarylhydrazine is

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• reaction mechanisms are disclosed if available. Keywords: alkyne; catalysis; cyclization; electrochemistry; five-membered ring; Introduction Organic five-membered rings, an essential class of organic compounds, not only are frequently used as important starting materials, intermediates or ligands in

• , this protocol was an efficient and sustainable approach to synthesize 2,3′-biindolyl atropisomers and could be potentially applied in manufacture of functional materials, bioactive molecules and chiral ligands. Construction of isoindolinones and indolizines An electrochemical and copper-catalyzed

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• exceptional potential as ligands targeting secondary structures of nucleic acids, particularly G-quadruplexes (G4) [21][22]. The indolo[1,2-c]quinazolin-6(5H)-one scaffold 1 exemplifies this design principle, with its rigid polycyclic framework mimicking topologies of established DNA/RNA-interactive molecules

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• ; carbonyls; NHCs; photochemistry; reduction; Introduction The introduction and exploration of N-heterocyclic carbenes (NHCs) ranks among the most important developments in chemistry research of the last 30 years [1][2][3]. In addition to their numerous valuable roles as ligands, including for important

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

• reactions, chemists have developed a series of catalysts composed of transition-metal cores and chiral ligands, which have been applied to various asymmetric reactions [50][51][52]. Compared to the enzymatic methods, the transition-metal-catalyzed approach may provide an advantage to access both enantiomers

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

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

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

• products, agrochemicals, and pharmacologically active compounds. Enantiomerically pure 1,2-diamines and their derivatives are also increasingly used in stereoselective synthesis, particularly as chiral auxiliaries or as ligands for metal complexes in asymmetric catalysis [1]. Metal-based reductants

• scaffolds that are commonly used as chiral ligands. In this context we report the development of a more sustainable method – which avoids the use of lead bromide or lead electrodes – employing an undivided cell with two glassy carbon electrodes for the electroreductive intramolecular coupling of aromatic

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

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

• versatility of this method in the asymmetric synthesis of diverse chiral molecular structures. Substituted [2.2]paracyclophanes represent another class of conformationally rigid, planarly chiral molecules, which have emerged as versatile scaffolds for developing chiral catalysts, ligands and functional

• DDD products 64e. Moreover, the authors showcased the facile derivatization of dimethoxy-substituted chiral DDD 64f into various DDD-based chiral ligands, such as the phosphoramidites 65, phosphoric acid as well as monophosphine ligands and diphosphine ligands 66. Notably, the applications of these

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

• replacing the azobenzene moiety of the already established partial agonist GluAzo with a diazocine unit. While both photochromic ligands show biological activity in the E form, the E-isomer is the thermodynamically more stable one for the azobenzene analog, whereas for the diazocine-modified

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

• bisoxazolines [1][2][3][4][5][6][7][8][9] and bisimidazolines [10][11][12][13][14][15] are efficient chiral ligands and have been widely applied in various metal-catalyzed asymmetric organic transformations. Various chiral bisoxazoline ligands have been prepared from diacids and enantiopure vicinal amino

• alcohols and utilized in different metal-catalyzed asymmetric organic reactions [1][2][3][4][5][6][7][8][9]. In comparison with bisoxazoline ligands, relatively less attention has been paid to bisimidazoline ligands [10][11][12][13][14][15]. Some well investigated bisimidazoline ligands are pyridine-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

• -affinity host–guest interactions between PA5 and these groups (mainly through phosphonate-quaternary ammonium ion pairing) [90]. Azobenzene guest molecules can achieve dual functions (on and off) as ligands through photo-induced cis-trans isomerization. Using pillar[6]arene as the ion channel, the host

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

• others (11–19) (see Figure 1), which may serve as virulence factors [8][9][10][11][12][13]. Most significantly, some of these indoles have been shown to be potent aryl hydrocarbon receptor (AHR) ligands [8][9][14][15], which can lead to induction of melanocyte apoptosis and inhibition of neutrophil

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 chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

• = 365 nm. Using this novel approach, α,α-1,1'-linked Gal-Fuc thiodisaccharides, designed as bispecific ligands for the Pseudomonas aeruginosa lectins LecA and LecB, which play key roles in host cell adhesion and exhibit cytotoxic effects, were successfully synthesized [120]. Tetraacetylated α-galactose

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

• identified. While the employment of L9 afforded endo-selective [3 + 2] cycloadducts 60, using Trost ligand L10 resulted in a complete reversal to the exo-cycloadducts 61. DFT calculations were performed and indicated that these two ligands act in different ways in the cyclization process, providing

• chiral products, e.g., biological activities and utility as chiral organocatalysts or ligands, warrants greater attention. We anticipate that considerable efforts in these directions would be crucial for advancing this field and fully unlocking the synthetic potential of isocyanides in the preparation of

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

• substituent(s) at appropriate position(s) on the benzene rings [8]. Enantiopure planar chiral [2.2]paracyclophanes have been used as chiral auxiliaries and chiral ligands for transition metals in the fields of organic and organometallic chemistry [9][10][11][12][13][14][15][16][17][18][19][20]. In 2012

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

• 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

• , which provided the best yields in the scope. Moreover, the strong correlation of the yield with the electronic effects in aryl rings was clearly shown in the experiment with iodonium salt 1q (Scheme 3). We believe that the reason for the predominant transfer of the electron-poor ligands under the given

• transfer of a single aryl group from unsymmetrical diaryliodonium salts was demonstrated through the use of dummy ligands, such as 2,4,6-trimethoxyphenyl. Background and conception. Reaction scope of iodonium salts 1 and isonitriles. aReaction conditions: isonitrile (0.2 mmol), iodonium salt 1 (0.2 mmol

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

• -amination of benzoxazoles by transition-metal-catalysed reactions that traditionally involve aryl halide scaffolds [11][12][13][14]. However, these procedures entail disadvantages that need to be overcome if green chemistry criteria are to be met; high temperatures, long reaction times, the need for ligands

• of azolic substrates, but here the amines and the ligands are still used in excess and auxiliary oxidants are occasionally employed [33][34][35]. Although electrophilic amines, such as chloroamines [36][37], hydroxylamine [38][39][40], acylated hydroxylamine (with a wider reaction scope) [41][42][43

• without the aminopropyl ligand. Under these conditions, only 48% of the product was obtained (Table 3, entry 13). This result demonstrates that the activity of the Cu catalyst is significantly influenced by the surrounding ligands. The amino ligand not only stabilises the catalyst, by ensuring stronger

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• yields of 1,2-thiazoles 3aa–ae are slightly lower (70 vs 78%) than by method A. We also investigated the effect of chiral catalysts or ligands in the reaction of thioamide 1a with 2a; however, we were unable to achieve high enantiomeric purity of product 3aa (see Supporting Information File 1, Table S1

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

• cases and worked very well for both aromatic and aliphatic amides, as well as sterically hindered oxetanes. The authors further proved the robustness of this reaction by preparing various bisoxazolines 189, compounds which are common bidentate ligands in asymmetric catalysis [99]. Over the years 2019

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

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

• that this approach does not allow us to predict the occurrence of the reaction, its yield, or confirm if the reaction might proceed via a different mechanism influenced by the substrate, catalyst, and ligands. Second, we assume that the reaction is controlled kinetically, where the activation energy

• simulating different solvent effects or examining the impact of different catalysts and ligands, extending beyond Pd(OAc)2. Additionally, accounting for varying reaction conditions, like conducting the reaction in acidic or basic environments, is possible by adjustments to the substrate-SMILES. Protonation