Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• literature. During our attempt to scale up the preparation of BPP 2 through the "DPEX" reaction, we unexpectedly obtained a 5-isopropoxy-substituted derivative of BPP (BPP-OiPr 3) (Scheme 1), whose structure was proven by NMR, mass spectrometry, and X-ray crystallography. In this work, we optimized the

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• ) gave more than moderate yields of the corresponding products. To evaluate the feasibility of the process in scale-up studies, gram-scale 2a was synthesized under optimized conditions. The reactions of 1a (1.760 g, 10 mmol) with H2SO4 (10 mmol) and TBAI (2 mmol) gave the corresponding 1,2-di-p

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• group developed the electrocatalytic racemic C(sp³)–H alkynylation of THIQs with terminal alkynes in a continuous-flow microreactor using copper/TEMPO relay catalysis [51]. The electrocatalytic reaction in continuous flow facilitates straightforward scale-up and demonstrating a broad substrate scope. In

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• 50 °C in isopropanol just after a couple of hours. The racemization barriers of the products were only slightly higher (28 kcal/mol) than the minimal requirement for separation of atropoisomers (24 kcal/mol). Scale-up done on the one-mmol-scale provided the corresponding product in comparable yields

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• . [6], and Sagmeister et al. [7]. The first two offer valuable perspectives on chemical reaction optimization, particularly focusing on process scale-up, while the latter discusses the potential of flow platforms for self-optimization reactions. Additionally, we refer the readers to the following

• model for scale-up within approximately eight hours. Their platform consisted of a flow reactor connected to an in-line FTIR spectrometer. In addition, the platform has two valves that allow a stream of reagents or target product to bypass the reactor coil directly into the in-line FTIR spectrometer

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• reaction of isocyanoacetates and saccharin-derived 1-azadienes. Enantioselective squaramide-catalyzed asymmetric IEDADA reaction of benzofuran-derived azadienes and silyl (di)enol ethers. Scale up and derivatizations of benzofuran-fused 2-piperidinol derivatives. Dihydroquinine-derived squaramide-catalyzed

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• material. Concurrently, implementing a scale-up synthesis procedure to exploit the application potential of rotaxane-based polymers induces structural ambiguities, thereby presenting a significant trade-off between realizing inexpensive production and defined structures. To overcome this rotaxane-synthesis

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• (Scheme 4A). Pleasingly, the scale up of the reaction was smoothly conducted. Under standard reaction conditions, product 2a (1.2 g) was afforded starting from 1a (1 g), showcasing the robustness of the transformation (Scheme 4B). Intrigued about the nature of the active source of SCF3 in the

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• to scale-up due to their violent reactions at elevated temperatures. Our protocol involved mild conditions, and to our expectations, a gram-scale conversion of 3ba to 4ba proceeded smoothly without appreciable loss in the reaction yield (Scheme 3). The reduced reaction time and a lower reaction

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• the case of an aliphatic terminal alkyne, such as dec-1-yne (1d), the 19F NMR study indicated 46% yield with method A (Table 2, entry 5), but it was difficult to purify and isolate product 2d because of the low molecular weight. Scale up conditions of method A, for the purpose of the isolation, led to

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters and β-keto amides by simply changing reaction conditions. These features, including a good substrate scope, excellent yield and selectivity and ease of scale-up, rendered the green hydrolysis reaction very environment-friendly, practical, and attractive. Experimental 1H and 13C{1H} NMR spectra

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• conditions (Table 1, entry 9). Other organic nitrogenous bases were tested (Table 1, entries 10–12). Et3N gave nearly the same result, while DBU seemed less efficient. The use of the inorganic base K2CO3 resulted in poor outcomes. With the optimized conditions in hand, a scale-up was successfully performed

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• materials have potential to be used as catalysts and sorbents. Further, these materials may be obtained in significant quantities since the method for the production is simple and does not include stages that are difficult to scale up. Thus, the method we have proposed has good prospects for practical

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

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

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• [26][29]. In order to demonstrate the synthetic utility of our methodology, we performed a scale-up reaction with representative starting materials, viz. 1a and 2b on a 1.0 mmol scale (Scheme 3). The reaction required slightly more time and resulted in the corresponding double and triple Michael

• reported in due course. Biologically active derivatives of cyclohexanones. X-ray structure of 4a (CCDC 2351387). Origin of stereoselectivity in the double Michael addition. The Michael donor–acceptor reactivity of curcumin: previous vs present work. A plausible reaction mechanism. Scale-up reaction

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• scale-up, are the advantages of using a flow system. In addition, reproducibility in a liquid–liquid flow system is improved because the flow velocity and temperature can be precisely controlled by using a syringe pump and a temperature control unit, respectively. Moreover, as the reaction mixture

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• fluorination of primary, secondary and tertiary benzylic substrates. The methodology was amenable to scale up, demonstrating the gram-scale synthesis of product 15 in 85% yield. The authors recognised the difficulty in sequential fluorination and noted that the use of a more electron-rich photocatalyst would

• showed they were able to scale-up and selectively fluorinate the ibuprofen methyl ester at the methylene group to produce over 2 g of product 12. The utility of the benzyl fluoride products as strategic intermediates for benzylation of electron-rich arenes was demonstrated by the authors (Figure 41B

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation. Keywords: aniline; (E)-2-arylidene-3-cyclohexenone; imine condensation; isoaromatization

• further demonstrated. As depicted in Scheme 5, we first attempted scale-up synthesis of product 4aa. Pleasingly, when starting from 2a on a 6.0 mmol scale, the product 4aa was afforded in 74% yield. We also conducted the successive synthesis of 4aa in a manner of one-pot procedure. On the condition of

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• mmol), scale-up experiments were conducted. The isolated yield of 4b (1.26 g, 90% yield) is quite satisfactory, as can be seen from Scheme 3. For the fluoroalkoxylation, we propose the mechanism given in Scheme 4. In this mechanism, first the double bond in (+)-camphene attacks the fluorine in the

• alcohol in 2 mL of CH3CN at 90 °C for 2 h. Isolated yields. Scale-up experiments. Reaction conditions: (+)-Camphene (1b) (1.0 g, 7.34 mmol), selectfluor (3.12 g, 8.81 mmol), MeOH (17.62 mmol), CH3CN (20 mL), 90 °C, 2 h. Proposed mechanism for fluoroalkoxylation of (+)-camphene by Wagner–Meerwein

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• selenocyanated products 3a–o achieved in acceptable to good yields. Similarly, the selenocyanation of C3- and C5-unsubstituted substrate 1p regioselectively furnished the 4-selenocyanated pyrazole 3p in good yield. The utility of this approach was further demonstrated by a scale-up experiment. When 10.0 mmol of

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this

• , providing another type of hybrid allylPd radical IV. After the equilibrium shifting to the π-allyl complex V, the unsaturated γ-AA derivative 6 would be obtained with the nucleophilic attack of amine 3. The utility of this protocol was further highlighted by scale-up reactions and diverse derivatizations of

• the first reaction mode for a difunctionalization of alkenes with diazo compounds via a radical-polar crossover process. This synthetic transformation proceeds under mild reaction conditions and shows high functional group tolerance. The studies on late-stage functionalization, scale-up reactions, and

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• scale-up of the HPW-catalyzed GBB reaction (5.0 mmol) between 2-aminopyridine (1a), 4-nitrobenzaldehyde (2a) and cyclohexyl isocyanide (3) in EtOH under μw heating. Plausible reaction mechanism for the HPW-catalyzed GBB reaction. Optimization of the reaction conditions.a Comparison of reaction

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• quinuclidine to direct fluorination reactions of 1,3-diketone and 1,3-ketoester substrates using fluorine gas can give difluorinated products by a simple batch process, offering a potentially valuable route to the synthesis of difluoromethylene compounds that is suitable for inexpensive scale-up. Results 2

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• atmosphere. Isolated yields. Substrate scope of amines. Reaction conditions: alkylthianthrenium salts 1 (0.3 mmol), amines 2 (0.2 mmol), DIPEA (0.4 mmol) in 2.0 mL of MeCN at 80 °C for 16 h under air atmosphere. Isolated yields. Scale-up reaction. Optimization of the thioetherification of S-(alkyl