Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• limitations in terms of substrate scope, stereoselectivity, and scalability, leaving ample room for innovation in catalyst design and mechanistic understanding. Fan and co-workers have long been dedicated to the asymmetric catalysis of chiral diamine ruthenium complexes. In 2020, they reported the efficient

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• % yield. Compared to the previous dianion approach, the developed process produced ethylmaltol (1) with a significantly improved purity profile and without the need for sub-zero temperatures. The scalability of this process was showcased by conversion of 10 g maltol (2) to 5.7 g ethylmaltol (1

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• very important, as it overcomes one of the major obstacles to the sustainability and scalability of organic electrosynthesis: the need for a supporting electrolyte in addition to reactants. The synthesized nitro-NNO-azoxy arenes were discovered as a novel class of fungicides, with in vitro activity

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• nitro source. The catalytic system demonstrates a satisfactory substrate scope and excellent regioselectivity. The scalability of the reaction was demonstrated, further underscoring the robustness of the protocol. Overall, this study highlights the potential of palladium-catalyzed C–H activation

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

• tolerance, and scalability [80]. Electrochemical methods offer the opportunity to tune reaction conditions by controlling parameters such as potential, current, electrode, and electrolyte [81], providing a sophisticated platform for attaining optimal reactivity. A variety of catalytic strategies can be

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• spectra are provided in Supporting Information File 1. To evaluate the scalability of this protocol, we performed the synthesis of diazepine 8a on a gram scale with 10 mmol of 1a, which led to the formation of product 8a in 91% yield (Scheme 8). Conclusion We have developed a new synthetic method to

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

• ][94]. Electrochemical transformations used renewable and clean electricity as a source of electrons and electron holes to generate radical species, showing several superiorities such as safety, economy, high selectivity, scalability, mild reaction conditions, powerful efficiency, environment-friendly

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

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

• the batch reactor (Table 2). The scalability of the reaction was further demonstrated by performing the electroreduction of diimine 1d on a 2.5 mmol scale under flow conditions. Compound 2d was obtained in 52% isolated yield achieving productivity and STY values that were 10.4 and 184.7 times higher

• . Significantly higher productivities and space-time yields were achieved under continuous conditions compared to the batch process. Furthermore, the scalability of the reaction was successfully demonstrated, highlighting its potential for larger-scale applications. Experimental General procedure in-batch

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

• features of this protocol include the use of O2 as an ideal, green oxidant, operational simplicity and scalability, high atom- and step-economy, and cost-effectiveness, collectively enabling the single-step synthesis of two medicinally relevant N-heterocycles in excellent combined yields. Keywords: C–C

• 6-bromo-2,4-diphenylquinoline (3g), both recognized for their antifungal activity [10], were successfully synthesized on a gram scale, showcasing the scalability and efficiency of the process (Scheme 3). After having demonstrated the broad substrate compatibility and the synthetic potential of this

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

• intent of using the benzyl group to protect the indole nitrogen rather than the Boc group. However, Pd-catalyzed hydrogenation of 25d led to a mixture of products, of which some were consistent with reduction of the indole ring. With respect to the scalability of the synthesis, the reactions can be

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

• tubular, continuous tank, bubbling and injection nitration reactor – directly governs thermodynamic control, product distribution, process scalability, and quality assurance [4][5]. Batch systems remain prevalent for low-throughput fine chemicals due to their operational flexibility, whereas continuous

• assess their advantages, limitations, and scalability potential in miniaturized systems [16]. However, a large number of literature cases on continuous-flow nitration reactions has emerged over the past decade, and there is a lot of general content that can be summarized from the research on continuous

• profiles, heat transfer characteristics, inherent safety protocols, and economic scalability parameters. Process parameters: The implementation of continuous-flow nitration processes rely on the precise control of multiple interdependent parameters, including but not limited to residence time, reaction

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

• view of these results, it seems evident that six-membered cyclic amines have the optimal ring size for the photocatalyzed enaminone formation process. For enaminones 9b–k the remaining mass balance comprised mainly unreacted starting materials. The scalability of the process was demonstrated in

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

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

• promoted by visible light at room temperature, requires no protecting atmosphere or additives, and the resulting polysubstituted oxetanes are obtained in moderate to good yields. Additional advantages include scalability and high chemoselectivity as various functional groups were tolerated, including

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

• and operational scalability [9][10]. Moreover, a high temperature and additive oxidants are generally required, which would limit the substrate scope. The hydrogen atom transfer (HAT) process has emerged as a powerful avenue for addressing these challenges, leveraging the HAT reagents to selectively

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 synthesis commenced with the treatment of precursor 92, obtained in three steps from ethylene glycol, with MeMgBr and catalytic 94/CuBr, yielding the 1,4-addition product 93 in 96% yield and excellent regioselectivity (ee 98%) (Scheme 15). The authors highlighted the scalability of this reaction

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

• overcoming scalability challenges in quantum technologies. Despite their potential, achieving high luminescence quantum yields has largely been limited to donor-functionalized monoradicals, and a detailed understanding of the luminescent behavior of open-shell organic molecules remains elusive. This review

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• position 4 of β-carboline by cross-coupling reactions. Thanks to its scalability, this novel approach ensures a broad accessibility to the target compound for potential pharmacological measurements. Using detailed NMR studies, the NMR signals have been assigned for both the base and its dihydrochloride

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

• electron-withdrawing groups. In 2024, Wang et al. [62] reported an electrochemical method for the synthesis of phosphorylated indoles in the presence of Cp2Fe as the mediator under mild reaction conditions without the need for external oxidants. This method improves the scalability of the resulting

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• utility and scalability [9][10][11][12][13][14][15][16][17][18][19][20]. Cyclobutane-fused tetrahydroquinolines (THQs) have garnered significant attention in drug discovery due to their inherent structural rigidity and enhanced pharmacological profiles [21], which render them highly desirable for

• intermediates, followed by intermolecular cyclization and aromatization. The scalability of this method was demonstrated through a gram-scale reaction, highlighting its potential for practical applications in medicinal chemistry and drug discovery. Synthetic strategies for the construction of

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• the scalability of the method, and 470 mg of 2-aminoproline derivative 6j was obtained in a single electrolysis batch. The wide application of unnatural amino acids in the design of peptidomimetics prompted us to examine the suitability of the developed conditions for dipeptide synthesis. Gratifyingly

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• attractive for industrial applications, where both scalability and robustness are essential. Beyond its practical advantages, the method offers notable versatility, enabling the conjugation of a wide range of aryl linkers to Cys residues. This flexibility is crucial for the development of ADCs, where precise

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• ” aspect of the protocol under microwave irradiation conditions, which enables rapid conversion of the starting materials to the products in water – a green solvent – in less than two hours makes this protocol an expedient and environmentally benign synthesis of hydantoins from amino acids. The scalability

• of this process is promising, driven by its simplicity, moderate to high yields, and the use of environmentally friendly reagents. Notably, microwave-assisted one-pot reactions eliminate the need for column chromatography, a common step in traditional purification methods but limits scalability

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• , as a beam of light traverses through a solution, photons are quickly absorbed, resulting in abrupt reduction in light intensity. Thr Beer–Lambert law imposes the most stringent constraints from a practical point of view, mainly in terms of scalability. This requires highly diluted solutions, which in

• operator variability, limited throughput (and, hence, scalability), and challenges in reproducibility. This approach is not operated in continuo: grinding and irradiation occur sequentially and not simultaneously. Vortex shakers (Figure 2b), which provide circular motion for mixing, are cheap, user

• . Looking forward, designing specialized equipment capable of integrating both mechanical impact forces and photon input would be highly beneficial. Moreover, a major challenge limiting the widespread adoption of mechanochemistry in industrial applications is scalability [80], a concern that also extends to