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

• there was a weakly basic counter anion with excellent displaceability, such as trifluoroacetate or sulfonate, the nitrenium refused to engage with the pendant alkene, and complex mixtures, presumably containing N-N dimeric products of starting material, were observed. During reaction optimization, we

Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• share their data, to take advantage of recent advances in machine learning (ML) for synthesis planning, reaction optimization, and property prediction [30][31][32]. The discoverability and reusability of data, especially by machines, is central to the ‘FAIR Guiding Principles for scientific data

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

• scrambling.a Reaction optimization of intramolecular [2 + 2] cycloaddition.a Supporting Information Supporting Information File 52: Experimental section, characterization, and copies of spectra. Acknowledgements We thank Eduardo Garcia Alonso for preliminary results and Dr. Roza Bouchal for help with cyclic

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• investigation into whether such moderate activation strategies could facilitate copper-mediated coupling reactions of sterically demanding alkylboronic esters under mild conditions. After thorough reaction optimization, t-BuLi emerged as the superior activating agent, outperforming other organolithium compounds

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

• chemical reaction optimization has been enabled by advances in lab automation and the introduction of machine learning algorithms. Therein, multiple reaction variables can be synchronously optimized to obtain the optimal reaction conditions, requiring a shorter experimentation time and minimal human

• reactors; data processing; high-throughput experimentation; machine learning; reaction optimization; Introduction Organic synthesis plays a crucial role in drug discovery, polymer synthesis, materials science, agrochemicals, and specialty chemicals. Their synthesis and process optimization require

• tasks and reducing the overall process development lead time [3][4]. A standard workflow and general methodology for organic reaction optimization through ML methods is shown in Figure 1. The workflow comprises (i) careful design of experiments (DOE); (ii) reaction execution with commercial high

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• equiv of 1 (Table 1). We also demonstrated that this procedure can be performed on a 4.0 mmol scale (with respect to SF5Cl) to provide access to ≈0.5 g of 2 in 43% isolated yield. Additional details on reaction optimization can be found in Supporting Information File 1. Upon increasing the equivalents

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• efficiency and effectiveness of reaction conditions design, and enable novel discoveries in synthetic chemistry. Keywords: data preprocessing; reaction conditions prediction; reaction data mining; reaction optimization; reaction representation; Introduction Machine learning (ML) techniques have been widely

• conditions prediction and local reaction optimization, which use the structures of reactants and products as inputs to predict their corresponding targets, require suitable choices of reaction featurization. The common methods can be categorized into three types: (1) descriptor-based, (2) graph-based, and (3

• individual synthetic step. To further improve yields, it is necessary to perform local reaction optimization, which is discussed below. Local reaction optimization ML-guided local reaction optimization, or self-optimization, is an automated and generalizable approach that can accelerate the discovery of

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• /cis dr was determined by 1H NMR analysis of the crude reaction mixture. Intramolecular cyclization of β-lactams induced by photoredox conditions.a Supporting Information Supporting Information File 122: Reaction optimization studies, general experimental procedures, product isolation and

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• 94%, initial reactant concentration of 0.5 mol/L, reaction temperature of 40 °C, molar ratio of reactants at 4.4:1, and a residence time of 12.36 minutes. Keywords: continuous flow; kinetic modeling; nitration; reaction optimization; static mixer; Introduction The demand for high-quality

• continuous flow nitrification system, leading to better elimination of the effects of mass and heat transfer [11]. Kinetic modeling is a classical approach to chemical reaction optimization, where the effects of various reaction parameters on the results are effectively quantified by mathematical formulas

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

• or its equivalent is indirectly prepared and utilized in only solution phase. Results and Discussion First, we have chosen hex-5-yn-1-ylbenzene (1a) as the model substrate in the reaction optimization (Table 1, method A). The reaction was carried out as follows: Hex-5-yn-1-ylbenzene (1a, 0.5 mmol

• ) was reacted with the Brønsted acid (X equiv) and the fluorine source (Y equiv) in the solvent (4 mL) at temperature of T (°C) for Z hours. The chemical yield of the desired product, (5,5-difluorohexyl)benzene (2a), was evaluated for reaction optimization by using the 19F nuclear magnetic resonance

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• ). Results and Discussion Reaction optimization Over the past two decades more than 300 various catalytic systems have been proposed for Biginelli chemistry, e.g., simple inorganic and organic acids, metal salts, metal oxides, ionic liquids, phosphines, nanocatalysts, organocatalysts, ion exchange resins [1

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• acids). In order to expand DELs to the GBB reaction, compartmentation was proposed to confine an acidic catalyst into the lipophilic core of micelles, inaccessible to water soluble DNA. Micelles were made of a sulfonic acid substituted, amphiphilic copolymer 13. After reaction optimization, a narrow

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• cycle for the hypervalent iodine-catalyzed amide and alkene coupling. Hypervalent iodine-catalyzed olefin difunctionalizations background. Amide and alkene reaction optimization studies. Supporting Information Supporting Information File 14: Spectral characterization of the products and kinetic studies

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• inhibitor (R)-rolipram (5b) [15], and the commercial drug (R)-baclofen hydrochloride (6), used to treat muscle spasticity from spinal cord injury and multiple sclerosis [16]. Results and Discussion Desymmetrization of N-protected 2,5-dihydro-1H-pyrroles Some initial results and reaction optimization Based

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• reagents as SOMOphilic alkynes but this only afforded a 29% yield of the desired product. After switching to a radical-polar crossover approach the yield could be significantly improved. Key to the reaction optimization was the reduction of the temperature to −20 °C and the addition of BF3·Et2O. A large

• Temperature screening.a Additive screening. Fine-tuning of the reaction conditions. Supporting Information Supporting Information File 68: General methods, photochemistry set-up, reaction optimization, experimental procedures and compounds characterization. Funding The authors thank the Ecole Polytechnique

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

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

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• . Reaction optimization studies.a The effect of Hantzsch esters and other reaction parameters.a Supporting Information Supporting Information File 4: Full experimental details and characterization data of all compounds. Funding We are grateful for the financial support provided by the National Nature

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• and aromatic nucleophiles in the one-pot transformation. aNot determined (mixture with unidentified products). Reaction optimization toward 4 (see also Scheme 2). Supporting Information Crystallographic data of compound 6 were deposited in the Cambridge Crystallographic Data Center under the CCDC

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• for low-cost and environmentally friendly aerobic oxidation and further optimized it to improve the reaction rate. Reaction optimization for aerobic oxidation under batch conditions Based on entry 3 in Table 1, we next focused on optimizing the reaction to increase the reaction rate (Table 2). Open

• aerobic oxidation using the honeycomb reactor. Flow setup for substrate scope and additional screening. Reaction screening for aerobic oxidation of 4-methoxybenzyl alcohol (1a). Reaction optimization for aerobic oxidation of 4-methoxybenzyl alcohol (1a). Evaluation of the reaction rate using various flow

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• to our previous study with the corresponding boronic acids [22]). Synthesis of both enantiomers of arylglycine building block 18. Reaction optimization. Supporting Information Supporting Information File 176: Experimental section and characterization data. Funding Financial support by the research

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• (Scheme 12) by an earlier procedure developed by us [51] in order to investigate the reaction optimization by HPLC–UV. Then, the reactant scope of the reaction was explored by involving to the reaction APBTTs 1a–h, bearing various aroyl substituents, and benzylamine (Scheme 13) [55]. As a result, we found

• us [51] in order to investigate the reaction optimization by HPLC-UV. After that, the reactant scope of the reaction was explored by involving to the reaction APBTTs 1a–h, bearing various aroyl substituents, and arylamines 11a–d, bearing aryl substituents with various electronic effects (Scheme 18

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• only in modest amounts even after extensive reaction times (more than 3 days) and high catalyst loadings (30–35 mol %). After reaction optimization, use of G-II catalyst allowed formation of cyclooctene 58 in excellent 90% yield. This compound could ultimately be advanced to 59 in 8 steps. Exhibiting a

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• Discussion Key elements of reaction optimization are summarized in Table 1. With NaI (20 mol %) and PPh3 (20 mol %), acrylamide 1a and redox-active ester 2a were used as model substrates to react for 36 h in acetonitrile (MeCN) under blue LEDs irradiation and N2 atmosphere, delivering the desired oxindole

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• olefinic oxindole 4a shown in Table 1. In our continuous effort on the reaction optimization of benign solvents, we firstly evaluated the influence of reaction time and protic solvents such as EtOH, iPrOH and MeOH at 25 °C for 6 h, which only results in slightly different LC yield (93–95%) of compound 3a