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

• ][17][18][19][20][21][22][23] and more [24]. Especially BINOL-based crown ethers proved to be highly useful and were applied for stereoselective molecular recognition [25][26][27], for catalysis [25][28][29][30][31], as stationary phases for chromatography [32][33][34], but also as building blocks for

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

• that its sufficient acidity is key to the success of the reaction. Using the 2N-Troc-protected GlcN phosphite 44 as the donor and the 4,6-O-benzylidene acetal-protected 1,2-diol 45 as the acceptor afforded the β,α-disaccharide 46 with high stereoselectivity under borinic acid catalysis [62]. In

• '-Disaccharides were also synthesized using glycosyl organoboron catalysis and employing 1,2-diols as acceptors, while activation of the glycosyl donor was facilitated by the "acidic" C2–OH group of the borinic acid-complexed acceptor moiety [63]. For instance, the phosphite donor 35 was coupled with a Man

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

• 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

• system is more efficient than the earlier described usage of the pure NaH2PO2: higher solubility of the potassium, rubidium and cesium salts compared to the sodium and lithium and a proper pH of the reaction medium. Acidic catalysis strongly accelerates the rate of hemiaminal and iminium ion formation

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

• attention due to its broad applications in various fields, including but not limited to drug discovery, asymmetric catalysis, and materials science (Figure 1b). Consequently, the development of efficient and stereoselective methods for assembling such scaffolds with respect to structural diversity has

• high enantioselectivities. Beyond planar and axial chirality, the same group developed a three-component coupling reaction of 2,2′-diisocyano-1,1′-biphenyls 16, aryl iodides, and carboxylates (Scheme 3a) [30]. Under chiral palladium catalysis, unique inherently chiral saddle-shaped bridged biaryls 17

• 34f could be used as the starting material to prepare the axially chiral olefin-oxazole 37, which might be a potentially useful ligand in asymmetric catalysis. A possible stereochemical model was proposed as well, involving synergistic activation of both the alkynyl ketone and isocyanoacetate by the

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

• Review article discussing photocatalysts capable of harnessing low-energy red light to trigger chemical reactions [19]. In addition to photoredox catalysis, several mechanistic platforms that leverage light – such as the use of electron donor–acceptor complexes [20], proton-coupled electron transfer [21

• ], hydrogen atom transfer [22], halogen atom transfer [23], and energy transfer catalysis [24][25] – have been established as powerful additions to the arsenal of photon-driven reactions. Three articles in this thematic issue exemplify this: The Molloy group developed an intramolecular [2 + 2]-cycloaddition

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

• consequence, the corresponding HOMO(diene)–LUMO(dienophile) energy gap becomes smaller, which, according to the frontier molecular orbital (FMO) theory, constitutes the origin of the observed acceleration (following the so-called LUMO-lowering concept in catalysis) [36][37][38][39]. This widely accepted

• as the relative Lewis acidity of the catalyst (measured by the Child’s method [41][42][43]), but do not follow the same trend as the energy of the LUMO(dienophile). This finding therefore challenges the traditionally used LUMO-lowering concept as the ultimate factor controlling the catalysis in these

• destabilizing 4-electron interaction with the diene and ultimately, in a lower activation barrier. The term “Pauli-repulsion lowering in catalysis” [51] was coined to describe this effect, which has been proven to be general and applicable not only to related LA-catalyzed pericyclic reactions (as shown in 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, in which 2H-azirines act as the annulation reagent. Keywords: annulation; azirines; benzothiophenes; indoles; nickel catalysis; Introduction 2H-Azirines represent a valuable class of nitrogen heterocycles that are widely used as versatile building blocks in organic synthesis. In particular, the

• reactions of intermolecular annulation of a variety of non-aromatic five- [4][5][6] and six-membered carbo- and heterocycles [7][8][9] with azirines, which occur under transition metal catalysis or photocatalysis. Annulation of the pyrrole ring to an aromatic system is limited to reactions of functionalized

• -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

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

• -(1→3)-Man ABz disaccharide. Yu glycosylation of the above ABz disaccharide with 3-OH in Man PVB 8 (0.9 equiv) under the catalysis of PhP3AuOTf at room temperature successfully gave α-Man-(1→3)-α-Man-(1→3)-Man PVB trisaccharide, which was further coupled with the poorly reactive C2–OH in mannoside 9

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

• . Control experiments, Figure S20). Conclusion In conclusion, a novel synthetic methodology for the preparation of benzamides from isonitriles and diaryliodonium salts has been proposed utilizing visible-light photoredox ruthenium-based catalysis. Both symmetrical and unsymmetrical diaryliodonium salts were

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

• Elena Fernandez Jaesook Yun Departament de Química Física i Inorgànica, University Rovira i Virgili, Tarragona, Spain Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea 10.3762/bjoc.21.109 Keywords: copper; copper catalysis; Copper catalysis continues to thrive as

• papers (three Full Research Papers and two Letters) contributed by scientists from Asia and Europe. The breadth of topics and the geographical diversity of the authors reflect the global interest in copper catalysis today. The Review article by Yang and Fang focuses on copper-catalyzed yne–allylic

• straightforward reactions. Complementarily, the Review article by Jang and Kim provides a deep understanding of recent advances in the combination of electrochemistry and copper catalysis for various organic transformations [3]. Their contribution elaborates various C–H functionalizations, olefin additions

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

• synthesis of various benzoxazole derivatives, demonstrating its versatility and practical applicability. Keywords: aerobic oxidation; copper; grafted silica; heterogeneous catalysis; microwave; Introduction 2-Aminoazoles are nitrogenous heterocyclic compounds of high relevance due to their biological and

• , to the best of our knowledge, this study represents one of the few examples of a heterogeneous catalysed copper-mediated C–H amination of benzoxazole. The pursuit for greener methodologies in organic synthesis and transitioning from traditional homogeneous catalysis to the use of heterogeneous

• catalysts for direct C–H amination processes could be a significant breakthrough in optimising these reactions. Despite recent progress in site-selective C–H functionalisation [49], most reactions have remained reliant on homogeneous catalysis due to its molecularly defined nature. By contrast, the

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

• , or selenium enables spectral tuning across the visible to near-infrared range, improved photostability, and dual-state emissive behavior. In parallel, significant progress in synthetic methodologies – including enantioselective catalysis, electrochemical cyclizations, and multicomponent reaction

• applications in asymmetric catalysis [1][2], molecular recognition [3], and organic electronics [4][5]. In recent years, the incorporation of heteroatoms – particularly nitrogen – into the helicene backbone, giving rise to so-called "azahelicenes", has emerged as a powerful strategy to modulate electronic

• ), pronounced chiroptical activity (|gabs| = 0.0054–0.0056), and substantial ΦF of 0.21–0.32 under both neutral and acidic conditions. This work exemplifies the power of transition-metal catalysis for constructing enantioenriched helicenes with tunable photophysical properties. These contributions from 2021

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• the C–C double bond, that most commonly require some form of catalysis. Thus, developing catalyst-free processes presents significant challenges, although there are few successful examples in the literature [44]. Similar to the dihydrobenzimidazoles above, the investigations here also started with an

• form of catalysis from simple acids to metal catalysts [46]. Similar to the previous examples, the first step was the optimization of the conditions using the esterification of benzyl alcohol (12a) with acetic anhydride (8) and acetic acid (13), respectively. The optimization data are summarized in

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

• catalysis and proceed through a double addition mechanism. In 2011, Mikami et al. developed a catalytic asymmetric oxetane synthesis from silyl enol ethers 89 and trifluoropyruvate 90 using a chiral Cu(II) complex (Scheme 24) [67]. Besides excellent yields, they also observed very high cis/trans ratios and

• amidine base catalysis (Scheme 25b) [69]. Although this methodology employs equimolar catalyst loadings, the products 100 are obtained with complete diastereoselectivity and mostly in moderate to good yields. As for the mechanism, it is assumed to be analogous to the NHC-variant. Four years later, Somappa

• unprecedented Fe–Ni dual catalysis (Scheme 36) [86], which constitutes a more versatile alternative to Minisci or Friedel–Crafts alkylations. The reaction couples mono-, di- and trisubstituted olefins with (hetero)aryl halides, and it was used to prepare a relatively large library of 3-alkyl-3-(hetero

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

• across diverse bond activation challenges, particularly in C(sp³)–H, C(sp²)–H, S–H, Ge–H, and B–H bond transformations. The proposed system architecture emphasizes synergistic reagent cooperation rather than isolated component performance, representing a paradigm shift in photoredox catalysis design

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

• quinolinone products. Beyond electrochemical protocols, photochemical activation – particularly visible-light photoredox catalysis – has become a powerful and sustainable strategy for generating carbon radicals under mild conditions. In 2023, Fan’s group discovered a radical cyclization of N-arylacrylamides

• with α-aminoalkyl radicals generated from tertiary arylamines using photoredox catalysis (Scheme 13) [9]. In this system, Ir[dF(CF3)ppy]2(dtbbpy)PF6 was used as a photosensitizer to trigger the α-C–H activation of N,N-dimethylaniline, generating an alkyl radical under 30 W blue LED (454 nm) irradiation

• versatility of photoexcited palladium catalysis in radical transformations. Furthermore, the method utilizes the readily available Pd(PPh3)4 complex as the sole catalyst, making it operationally simple and cost-effective. In 2021, Wang’s group introduced a novel transition-metal-free, aldehyde-free strategy

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

• bonds in organic chemicals. Therefore, their selective functionalization is essential for advancing the synthesis of complex molecules like pharmaceuticals, polymers, or agrochemicals [1][2][3]. Advancements in organometallic catalysis have facilitated significant progress in this area through C–H

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• step is energetically favorable. Other than furfural, thiophene-2-carbaldehyde (2s) was used for the GBB and N-acylation reactions to make 6t (Scheme 4). The IMDA reaction of 6t was carried out under the catalysis of AlCl3 in dichlorobenzene at 180 °C for up to 24 h, but no compounds 7t and 8t could be

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 significant role of asymmetric catalysis in their strategy, utilizing a copper-catalyzed asymmetric 1,4-addition and a ruthenium-catalyzed asymmetric ketone hydrogenation. Fragment 61 was synthesized in 15% overall yield across 19 steps, while fragment 62b was achieved in 32% yield over 11 steps

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• of racemic and optically active functionalized cis-2,5-diaryloxazolidine derivatives [13][14][15][16]. Racemic cis-2,5-diaryloxazolidine derivatives were prepared under the catalysis of zinc triflate or nickel diperchlorate (Scheme 1a) [13][14]. Later, highly enantiomeric cis-2,5-diaryloxazolidine

• derivatives were obtained under asymmetric catalysis with a Ni(II)–bisoxazoline complex [15] and a Nd(OTf)3/N,N'-dioxide/LiNTf2 delay catalytic system [16], respectively (Scheme 1b and c). However, further exploration for convenient asymmetric catalytic synthetic methods is still in demand because the former

• -dicarboxylates from aldehydes and dialkyl 2-aryl-1-sulfonylaziridine-2,2-dicarboxylates under the catalysis of the readily available salen–Sc(OTf)3 complex (Scheme 1d). The salen ligand can be prepared in one step from enantiopure cyclohexane-1,2-diamines and substituted salicylaldehydes. Results and Discussion

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

• release (82). Numerous cinnamic acid derivatives with electron-withdrawing and -donating groups were converted to the corresponding amides 76–81 in moderate to excellent yields (Scheme 24B) [60]. 2.1.2 Transition-metal catalysis: Several transition metals have been exploited to catalyze O/N-acylations of

• cinnamic acid (7) to give amide 12 in excellent yield via Ti(IV)–O=C complex 102 (Scheme 31C) [69]. 2.1.3 Photocatalysis: Photoredox catalysis has gained much attention as a sustainable alternative approach to performing O/N-acylation by utilizing light as a renewable source. For example, Li and co-workers

• compounds and N-acylbenzotriazole 97 (Scheme 36) [71]. In this work, the photoactive [FeCl4]− formed in situ triggered silyl radical 119 generation, leading to N-silylamine 120 as the active amine nucleophile. 2.1.4 Metal-free catalysis: Despite the wide applications of metal-based catalysts in developing O

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• . Keywords: alkynes; catalysis; cyclizations; domino reactions; heterocycles; Introduction Pyrimidines and purines are one of the most important heterocyclic compounds with prevalent biological functions. Both are found in nucleosides and their corresponding polymeric DNA and RNA, and hence are vital for

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• column chromatography was required during this process, the synthetic route is highly practical. The enantioselective annulation of tertiary enamide 28 with enoldiazoacetate 29 was then explored under the catalysis of a chiral dirhodium catalyst. While Doyle and co-workers had previously reported an

• alkaloids, though it features a truncated cyclopentane rather than the characteristic cyclohexane or cyclohexene. In their optimization studies, the authors found the sequential catalysis of a chiral binol–Ti complex and BF3·Et2O to be the most efficient, providing products 39 in high yields with excellent

• -silyl substituted cyclopentanone 41, and acyl chloride 42 produced enamide 43. The polycyclization then took place under the catalysis of Cu(OTf)2/L3 and In(OTf)3, delivering tricyclic product 44 in high yield with excellent enantioselectivity. Despite formation of multiple diastereomers due to the

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80