pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• values that are not correlating well with the QM-computed pKa values, we find C–H sites that are either bridgeheads or where the negative charge is stabilized by resonance. This may be due to the nature of the chosen descriptor vector based on sorted CM5 atomic charges as it may not take into account

• 21.9 (the least substituted C–H next to a ketone). For more information, see Supporting Information File 1, section “Outliers for Reaxys”. When we evaluate our ML models on the whole out-of-sample set, we again find that the regression model (MCC of 0.82) outperforms the classification model (MCC of

• 0.70) when used as a binary classifier as seen in Table 2. While a direct comparison cannot be made between Roszal et al.’s results [3] and ours, we find our result to outperform theirs with an accuracy of 0.96. In general, it is surprising that the LightGBM regressor outperforms our LightGBM

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• different hypervalent iodine reagents for this reaction. To find the correlations between experiments and theoretical calculations, chlorination and bromination of 2-naphthol using PIFA/AlCl3 and PIDA/AlBr3 were carried out. Consequently, we found an excellent correlation between the yield and the energy

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• metal catalysis as a viable and potentially general approach for reaction discovery and would find broad application in new synthetic contexts. Decarboxylative cyanation: background and our working hypothesis. Scope of electrophotochemical decarboxylative cyanation of aliphatic carboxylic acids. All

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

• parameters. We hope that these potentially biologically active bicyclic fluoroalkoxy compounds will find a place in various application areas in biological systems. Organofluorine derived drugs. Oxyfluorination of benzonorbornadien (1a) with Selectfluor and alcohols. All reactions were carried out using 0.5

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• sources and thus as building blocks for synthesizing pyrazolyltriazoles by CuAAC reactions. To find a feasible approach to pyrazolyltriazoles of type 1 with a highly substituted scaffold, we decided to explore the benefits of a modification of the triazene-protected pyrazole core. In the next step, a

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• energy profile is seen for protonation-induced cyclization of 1, although the 6/6/6-tricyclic C3 tertiary cation is 7.1 kcal mol−1 higher in energy than its preceding intermediate (Figure 2C). A lower energy conformer of 1 exists, but we have been unable to find the corresponding cation A1b+, which

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• urgent need to find novel, effective and safe drugs for cancer therapy. Recently, focusing on the design of more potent anticancer drug candidates using more sustainable synthetic processes, we report a new Ugi four-component reaction approach for easy access to Ugi-derived isatin-peptoids in moderate to

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ] and the broad spectrum of biological activities. Among the five-membered ring compounds, we find indanone (1, Figure 1). Within the class of indanones, we can highlight some interesting compounds. For example, nakiterpiosinone (2), which inhibits the growth of P388 mouse leukemia cells with an average

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• -systems whose unsaturated bridge was extended using –CH2– and –NH– units exhibit the best storage energy capacities as well as the highest TBR barriers. It can be noted that we were unable to find the TS for the thermal back conversion of the type-Id system by employing CI-NEB and Gaussian 16. Several

• determined using the PBE/6-311++G** method utilizing the Gaussian 16. Thereafter, the relative energy profiles were generated by computing the electronic energies of the point structures at the (8,8)-CASPT2/6-311++G** level of theory. Attempts to find the TS (both with CI-NEB and Gaussian 16) for the thermal

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• numerous enhancements to the findability and interpretability of deposited glycan structures, yet crucial quality indicators are either missing or hard to find on the PDB pages. Without a way to access wider glycochemical context, problematic structures may be taken as fact by keen but inexperienced

• and, therefore, poorly resolved density regions, whereas in electron cryo-microscopy different conformations and compositions are averaged out during image classification and volume reconstruction [5]. Owing to these difficulties, it is not uncommon to find problematic carbohydrate structures in the

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• each method, enabling practitioners to quickly find the bioisostere and method that best suits their requirements. Physiochemical and biological data will also be discussed where available. Review Definitions and parameters for determination of (bio)isosterism We will distinguish between geometric

• are systems that widen accessible chemical space [73], have an increased number of stereogenic centres in accordance with Lovering's ‘Escape from Flatland’ approach [9], and could find application as alternatives to aromatic motifs in certain scenarios. Detailed discussion of their synthesis exceeds

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• , novel pharmaceutical systems, such as liposomes, microcapsules, and nanoparticles, were adopted to enhance the stability and bioavailability of these compounds [13][14][15]. To find a sustainable way of supplying crocins, researchers have developed various approaches to produce them, including plant

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

• attractive intrinsic properties, HPW was used in our initial studies to find the best reaction conditions. Additionally, knowing that a higher temperature is crucial for faster GBB reactions, μw heating was used, taking into account our experience over the years on the μw-mediated MCRs [51][52][53]. 2

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• reaction [9]. This technique has been used to find several new compounds from actinomycetes [10][11][12][13]. In the course of our PC screening for new natural products from rare actinomycetes, Saccharopolyspora sp. KR21-0001 produced a new compound 1, whose physicochemical properties, accurate mass and UV

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• (Table 2, entries 1 and 2; 4–22-fold increase in rate compared to CD2Cl2). We were unable to find any clear correlation between rate and a variety of solvent parameters; the success of mixed solvents suggests many factors are at play. Throughout our studies, we used CH2Cl2 and CD2Cl2 interchangeably

• with alkene but also the urea carbonyl. The Bronsted acidity of the urea would be increased by coordination to gold, and if such coordination is key to enabling reactivity, this would confirm the higher reactivity of urea 1a. The divergent behavior of sulfonamide 1d does not find an easy explanation

• effective in reactions that depend on hydrogen bonding activation [54], and the substrate effects observed here find some similarities in other Bronsted acid-catalyzed processes. In disulfonimide-catalyzed asymmetric intramolecular hydroamination of alkenyl thioureas, sulfonamides are unreactive compared to

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• actively and strongly prefers C2-substituted Gal, while RCA1 does not even tolerate these substitutions. Interestingly, we also find that fucosylation of the GlcNAc residue (as in Lewis antigen motifs) completely abrogates CMA1 binding (Figure S1, Supporting Information File 2), despite the presence of

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• the hole is closed restoring the original cage. Among the species that have been incarcerated with this procedure, we can find He, Ne, Ar, Kr, H2, N2, O2, HF, CO, CO2, H2O, H2O2, CH4, NH3, HCOH, HCCH, and CH3OH [26][27]. The encapsulation of atoms or small molecules inside the fullerene has been found

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• and reversible process named phase 1. We find that the barriers for the radical cation mechanism are significantly lower than those found for the neutral pathway. The peapod is mainly providing one-dimensional confinement for the reaction to take place in a more efficient way. Car–Parrinello

• slightly larger than 2 Å in all three cases. Finally, formation of dimer 1-Cs is exothermic for the radical cation profile, but moderately endothermic for the neutral dimer, as previously observed. As general trends, we find that the radical cation profiles are qualitatively parallel with some minimal

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• simulations were set up. First, hybrid GAGs (Figure 1) were prepared and docked using RS-REMD to find the pose in the binding site with the lowest interaction energy. Then, the GAG was pulled away from the binding site until it was shifted 40 Å from the starting position. Afterwards, the GAG was pulled in

• . The RMSD increased gradually up to values of around 40 Å during the unbinding process, and then decreased slowly when it was pulled in. After about the 20th window RMSD stabilized between 15 and 20 Å, suggesting that the GAG did not find the initial pose and was trapped in a different minimum (Figure

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• ]biphenylene (18). In their efforts to find a more general method for the synthesis of benzo[b]biphenylenes, Barton and co-workers were able to synthesize benzo[b]biphenylene (18) in 71% yield by the reaction of equal molar amounts of tetrabromo compound 16 and 1,1,2,2-tetrabromo-1,2-dihydrobenzocyclobutene

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• because it took some time to find the benchmark reaction needed to develop the catalysts (Figure 2) [2]. With this operational enolate chemistry in hand, it quickly became clear that increasing π acidity at the same time decreases the stability of the catalyst [3][4][5]. This suggested that induced rather

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• high electron mobility and efficient charge transfer. In particular, Qx derivatives find use as non-fullerene acceptors (NFAs) in OSCs and as essential building blocks in sensitizers for DSSCs. The significance of Qx extends beyond to thermally activated delayed fluorescence (TADF) emitters and

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• molecule is located. The assignment of the appropriate proton signals in the complex was achieved through the analysis of 1D and 2D NMR spectra (see Supporting Information File 1). Recently, an automated interaction site screening (aISS) procedure was used to find the optimal geometry of the forming

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• primary carboxylic acids but also secondary carboxylic acids (3n−s). We were pleased to find that cyclic carboxylic acids, including strained 3- and 4-membered rings, participated in this transformation and delivered the corresponding products in good yields. It should be mentioned that aromatic and more