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

• been characterized as an ideal solvent for click reactions, the limited solubility of most organic substrates could limit its application. Thus, the transformations of either water-insoluble or solid compounds require a solvent to establish high reaction performance, i.e. homogeneous solutions with low

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

• ]. Thus, the use of visible light as an energy source provides more efficient chemical transformations and minimize the use of harmful reagents, the generation of waste and the consumption of energy, fulfilling several principles of Green Chemistry and promoting greener opportunities for organic synthesis

• moieties, respectively, since they could enable further chemical transformations. Unfortunately, when 2-methyl-3-bromochromone was employed as the substrate, the process failed to afford the desired enaminone product, which was possibly caused by a combination of increased steric hindrance and decreased

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

• other transformations that can offer useful functionalities. These include ionization via protonation of one of the nitrogens forming the azo bond [12][13], azo–hydrazone tautomerization [14][15], and binding of analytes to side groups [16]. Such transformations depend on the azobenzene structure but

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

• with limited chemical transformations is highly desirable and should enable the discovery of new fusicoccane derivatives with improved biological activity. Inspired by the biosynthetic machinery of terpenoids, we have reported a hybrid synthetic strategy for accessing bioactive terpenoids by combining

• enzymatic terpene cyclization and chemical synthesis [30][31][32][33]. Briefly, the carbon scaffolds are forged by terpene cyclases, followed by concise chemical transformations to yield the desired natural products. Here, we describe heterologous biosynthesis of cotylenol by engineering the biosynthetic

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

• of benzamides (Scheme 1A) [6]. Over the years, the basic reaction has been modified to imply various metal-containing catalysts [7][8][9][10][11][12][13][14][15][16][17][18], metal-free transformations that employ heteroarenes under harsh conditions [19], or using diazonium salts as arylating agents

• [20][21]. However, diazonium salts are distinguished by their inherent instability complicating their use in such transformations. Moreover, among the various arylation strategies, photochemical methods remain relatively underexplored, with only a few examples reported [22][23]. These methods often

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

• one of the most dynamic and versatile areas of contemporary chemical research. Once viewed primarily as a cost-effective alternative to noble metals, copper has emerged as a powerful and versatile catalyst, capable of mediating a wide array of chemical transformations through both two-electron and

• single-electron pathways. This duality has enabled access to previously elusive molecular transformations, positioning copper at the center of modern synthetic strategy. This thematic issue captures the dynamic nature of the field, featuring five insightful Review articles and five original research

• 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

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

• ]. These data [1][2][3][4][5] inspired researchers to expand the chemistry of these compounds and to search for new synthetic methods and chemical transformations [14][15]. Unlike the aromatic congeners, the chemistry of non-aromatic dihydro-1,2-thiazoles is less represented in the literature [16][17][18

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

• additions and hydrolyses (in case of esters and amides), as well as epimerisations at the α-carbons, oxetanes are stable to such chemical transformations. In case of the gem-dimethyl group, which is commonly used to block metabolically labile sites at the expense of raising lipophilicity, bridging the two

• transformations of 3-oxetanone leading to advanced oxetane building blocks. In chapter 3, we review the reactivity of oxetanes with regards to ring openings and ring expansions including both symmetric and enantioselective variants. Finally, chapter 4 covers isolations, biological activities and total syntheses

• -, particularly 2-methylideneoxetanes have become valuable intermediates in oxetane chemistry as they readily undergo a variety of chemical transformations, including ring-opening reactions with nucleophiles, epoxidations, cyclopropanations and [3 + 2] cycloadditions with nitrile oxides [51][52]. In addition

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 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

• achieved using Suzuki and Sonogashira cross-coupling reactions. One of the first examples was the synthesis of diazuleno[1,2,3-cd:10,20,30-fg]pyrene, which was later subjected to on-surface transformations [94]. More recently, a more general approach was reported by Langer and co-workers, who described the

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

• rapid construction of complex molecular architectures. This review aims to summarize the diverse strategies for inducing intramolecular transformations of N-arylacrylamides using various carbon radical reagents, including methods initiated by photonic, thermal, or electrochemical processes, which have

• been extensively investigated by researchers. Keywords: carbon radical reagents; intramolecular transformations; N-arylacrylamides; oxidative difunctionalization; radical reactions; Introduction Alkenes, as abundant and versatile feedstocks, have been widely employed in organic synthesis

• transformations, (4) electrochemical approaches, and (5) metal-free or electron donor–acceptor (EDA)-driven systems. The substrate scope, limitations, and mechanistic aspects of these radical cascade cyclization strategies are critically examined. Review N-Arylalkenes: alkyl C(sp3)–H radicals Early investigations

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• various synthetically useful transformations, including alkene synthesis via Horner–Wadsworth–Emmons reaction [14][15], heterocycle construction [16][17], and the synthesis of chiral β-amino and β-hydroxy phosphonic acids [18][19]. Furthermore, they exhibit metal-complexing abilities [20], and anti

• efficiency, strong basic or acidic conditions, and excess of organohalides as starting materials. Recent years have witnessed the upsurge of free-radical oxidative phosphorylation transformations that became a reliable strategy for the construction of C–P bonds in organophosphorus chemistry [2][32][33][34

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

• activation, transforming these inert bonds into reactive carbon–transition metal (C–M) bonds. Subsequent transformations of these complexes enable the formation of an array of new functional groups, such as carbon–carbon and carbon–heteroatom bonds, underpinning a plethora of synthetic applications

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

• and deprotection steps, functional group transformations, stereocontrolled allylation, cross-metathesis, and Horner–Wadsworth–Emmons (HWE) olefination. This method highlights the power of catalytic stereocontrol, achieving the complex architecture of borrelidin fragments with efficiency and precision

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

• [5] and the FDA-approved antibiotic linezolid [6] (Figure 1). Both chiral oxazolidines [7][8] and oxazolidinones [9][10] have been utilized as chiral auxiliary groups in many asymmetric organic transformations. Oxazolidine derivatives have been prepared mainly from condensation of vicinal amino

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

• relatively new prima donna of functional groups explored in drug design, were smoothly prepared. 2.4 Miscellaneous reactions Cyclopropenone, the smallest Hückel aromatic system, has been subjected to the ring opening reactions, driven by the release of ring strain. Numerous transformations of cyclopropenone

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

• Isatin is a well-known natural indole derivative. Due to the broad biological activities of its derivatives, extensive research has been conducted on their synthesis. Furthermore, the isatin framework is a versatile starting material for various transformations, including multicomponent reactions and the

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

• efficient for related transformations [28][29]. However, only a yield of 15% of the desired product 4a was obtained after stirring for 15 hours, due to low conversion of the starting material. Subsequently, different mono- and bidentate ligands were tested. DPEphos was found to be the most potent ligand

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

• are operationally very simple and only use commercial I(III) reagents and sulfonic acids, amounting to a metal-free protocol for alkene amino-oxygenation. No special precautions need be taken to exclude air or ambient moisture, and the products are amenable to further transformations. Keywords

• trace of amino-alcohol product [34][35]. These transformations are likely difficult or even impossible in a single step with the products from our previously reported amino-trifluoroacetoxylation reaction, highlighting the utility of the present transformation. Conclusion In summary, we have developed a

• and only used commercial I(III) reagents and sulfonic acids. The products were quite stable in the reaction conditions and withstood standard purification protocols. No special precautions were taken to exclude air or ambient moisture, and the products were amenable to further transformations. We

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• power (E*red up to 1.5 V) can be classified as a bimodal photocatalyst. This type of molecule is capable of driving both oxidative and reductive reactions, thereby offering significant versatility to achieve photocatalytic transformations. To our delight, molecule 5a possesses a promising E*ox =−1.89 V

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• isocyanides, followed by a silver(I) triflate-catalyzed intramolecular heteroannulation of the resulting pyrazole-tethered propargylamides occurring in a 7-endo-dig fashion. The approach is scalable and tolerates a diverse range of substitution patterns. Keywords: heterocycles; post-MCR transformations

• heterocyclic peptidomimetics through various post-MCR transformations [28][29][30][31][32]. The construction of benzodiazepine cores has also been extensively explored through various post-Ugi transformations. In 2009, Torroba and co-workers developed a strategy towards β-turn mimetic benzo[e][1,4]diazepines 6

• heteroannulation leading to the pyrazolo[1,5-a][1,4]diazepine scaffold. Our initial choice was to investigate the use of silver(I) triflate (AgOTf) as a catalyst in toluene, given its previously demonstrated efficiency in various transformations involving the activation of triple bonds towards nucleophilic attack

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

• 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

• enantiocontrol. Metal control Over the past decade, the relentless pursuit of precision in natural products and pharmaceutical synthesis has driven remarkable advances in catalytic methodologies, particularly in the realm of catalyst-controlled chemoselective transformations [11][25][26][27][28][29]. In 2023

• the critical role of reaction medium polarity in modulating reactive intermediates, offering a strategic lever to toggle between C–H functionalization and reductive manifolds in photochemical transformations. In 2024, the Cheng group developed a palladium/chiral norbornene (NBE)-catalyzed cyclization

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• facilitated landmark organic transformations, such as the venerable Paternò–Büchi [6][7][8], Norrish–Yang [9][10][11], and enone–alkene cycloadditions [12][13][14], that proceed via the generation of a singlet or triplet diradical through the activation of an unsaturated bond [2][14]. While these seminal

• ). Pioneering studies have leveraged this platform with great effect, typically invoking π→π* transitions of conjugated alkenes to lower the bond order and generate a triplet diradical, primed for further reactivity. This key intermediate is pivotal in a plenum of synthetic transformations including geometric

• process (Figure 2B) [19]. In a bid to translate sensitization reaction probes to meaningful synthetic transformations, conventional intermolecular [2 + 2] cycloaddition reactions were initially trialled (Figure 3A). Preliminary reactions using styrene or methyl acrylate were unsuccessful, with no [2 + 2

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• quinazolinones, and the wide application of the chitosan-supported copper catalyst in various organic transformations [19][20][21], the use of chitosan-supported copper for quinazolinone synthesis has not been reported. As part of our ongoing research interest in chitosan and chitosan-supported copper catalysts

• in organic transformations [22][23][24], we intended to investigate the use of chitosan-supported copper as a catalyst for the synthesis of quinazolinones from 2-halobenzoic acids and amidines under mild reaction conditions (Scheme 1c). Results and Discussion The initial reactions commenced with 2

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

• conditions and shows broad applicability to di- and trisubstituted allenes. Its practicality is demonstrated through the gram-scale synthesis and functional group transformations of amines, amides, and lactams, emphasizing its versatility and synthetic significance. Keywords: α-quaternary nitrile; Cu

• remaining DIBAL-H and TsCN, ultimately yielding the cyanation product 5b in only 54%. The synthetic potential of the obtained β,γ-unsaturated nitriles featuring α-quaternary carbon centers was further illustrated using a series of transformations (Scheme 6). Nitrile 3q was hydrolyzed to amide 6 in a 90