Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• -naphthols 21 by using iodonium salts 16 as the source of the aryl group (Scheme 7) [61]. Through optimization, it was determined that the presence of Na2CO3 as base and cyclohexane as solvent facilitated the C–C cross-coupling reaction. The products were obtained in satisfactory yields using various

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

• reaction conditions, electron-enriched hydrazones provided the expected products in high yields (2a, 3a, 4a). Note, that in the case of the N-tosylhydrazone, further optimization reactions were required (for more details, see Supporting Information File 1), and reducing the temperature for the halogenation

• -trifluoroacetophenone as an internal standard. ND = not detected. Optimization of the reaction conditions.a Supporting Information Supporting Information File 28: Full experimental procedures, characterization of products, details of mechanistic studies, and spectral data. Funding This work has been partially

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• 6a via 3-CRs. Optimization of the reaction conditions.a Supporting Information Supporting Information File 26: General synthetic procedures and characterization and copies of 1H NMR, 13C NMR, FTIR and mass spectra. Funding We gratefully acknowledge financial support from the Research Council of

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• bulk THF (c = 1.0 M) activated by chlorotrimethylsilane (20 mol %) and 1,2-dibromoethane (60 mol %), then alkyl bromide (10 mmol), 80 °C, 16 h. a2-MeTHF was used as solvent. Scope of the reaction. Yield of isolated product is given. Optimization of the organozinc synthesis.a Supporting Information

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• through successive nucleophilic additions to the central carbon atom of DEMO. Cyclization of 4a quenched by D2O. Plausible mechanisms for the ring closure of 4. Hydration of the ethynyl group of 4a. Optimization of the reaction conditions for the reaction of 1a with the lithium acetylide of 3a. Addition

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• wondered about reactions of mechanochemically generated difluorocarbene with simple acyclic ketones. The results and observations of this study are summarized here. Results and Discussion For the optimization of the reaction conditions, 4-methylacetophenone (1a) was chosen as model substrate. Under

• NMR spectroscopy using 1,2-dichloroethane as internal standard. Optimization of the reaction conditions.a Supporting Information Supporting Information File 12: Experimental procedures, optimization studies, compound characterization data, NMR spectra, and mechanistic investigations. Funding General

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrin architectures, which could be used in supramolecular assemblies, catalysis, or sensing. In this work a library of arm-extended dodecasubstituted porphyrins was synthesized through the optimization of the classic Suzuki–Miyaura coupling of peripheral haloaryl substituents with a range of boronic

• of equivalents of boronic acid (Table 1, entries 10 and 11). Coupling at the meso-meta-phenyl position Optimization of conditions for OET-meta-BrPPs 12 (Scheme 3) were investigated next. Table 2 summarizes the reaction conditions used to synthesize a library of OET-meta-arylPPs as shown in Scheme 3

• . Borylation and subsequent Suzuki–Miyaura coupling of porphyrin 13. Optimization table for the Suzuki–Miyaura coupling reactions with porphyrin 13. Optimization table for the Suzuki-coupling reaction on porphyrin 12. Optimization table for the Suzuki-coupling reaction on porphyrin 11. Optimization of the

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• yield of 88% each step). Since, during the optimization of the reaction conditions, we have noticed a certain instability of the spiro-compounds through chromatography on silica gel, we have initially carried out the purifications using alumina as the stationary phase. However, during the scope studies

• mechanism. Initial investigation of the GO-promoted oxidation/3C-Ugi reaction process. Investigation of the one-pot four-step synthesis of spiro[indole-THIQ] 3a. Gram scale reaction for the synthesis of spiro[indole-THIQs] 3. Supporting Information Supporting Information File 22: Additional optimization

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• -dioxane/water 5:1, 100 °C, 1 h. Scope and isolated yields of the synthesis of 5. Reaction conditions: 4 (1 equiv), p-TsOH·H2O (20 equiv), toluene, 100 °C, 4 h. Proposed reaction mechanism of the cyclisation with N,N-dimethylanilino functional groups. Optimization of the synthesis of 5a. Photophysical data

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• chlorine atoms as reported by Hosoya and Niwa et al. In this study, we investigated the synthesis of fluoroalkenes 2 or fluoroenynes 3 by Suzuki–Miyaura or Sonogashira cross-couplings with a key building block 1 (Scheme 1D). Results and Discussion Optimization of the conditions of cross-coupling reactions

• -containing building blocks. Optimization of reaction conditions for Suzuki–Miyaura cross-coupling using multihalogenated vinyl ether 1a. Optimization of reaction conditions for Sonogashira cross-coupling using multihalogenated vinyl ether 1a. Cross-coupling reactions between multihalogenated vinyl ethers 1

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

• . Synthesis of 3-arylbenzofuran-2(3H)-ones. Synthesis of 2-hydroxybenzophenones. Gram-scale experiment. Control experiments. Optimization of reaction conditions.a Optical properties of the compounds 4aa–ma. Values of [EE(λ) × I(λ)] used in calculating the SPF. Supporting Information Supporting Information

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• appears unfavorable in comparison to a single water dimer and single water molecules located on the narrow rim (γ-CD–3H2O (b)). The first layer of water molecules is filled by three water molecules in the plane of the narrow rim, and the fourth incoming guest is displaced into the cavity upon optimization

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• : 3a (1 mmol), CDI (0.49 g, 3 mmol), DBU (0.17 g, 1.1 mmol), MeCN (7 mL). Proposed reaction mechanism for the formation of products 4. Synthesis of derivatization products 7 and 9. Optimization of the reaction conditionsa. Supporting Information Supporting Information File 141: General information

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• borylation under an argon atmosphere. Radical-trapping experiments using TEMPO as a radical scavenger. A proposed reaction pathway for the synthesis of arylboronates. Optimization of the reaction conditions for synthesis of 3a from BiPh3 (1a) and (pinB)2 (2). Supporting Information Supporting Information

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

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• details in Supporting Information File 1, Table S1, entries 10–18), it was discovered that a combination of ACN/DMSO/H2O solvent, K2S2O8 oxidant, Ru(bpy)3Cl2·6H2O photocatalyst, and 28–34 °C temperature were the best-suited and optimized reaction conditions. After optimization, our efforts were put

• (see details in Supporting Information File 1, Table S2). In this context, our previously in-house-developed liquid–liquid extractor was utilized (see details in Supporting Information File 1, Figure S4) [27]. After few trials towards optimization of extraction and separation, the best yield (82%) was

• mechanism for the photochemically induced Achmatowicz rearrangement. Strategies for Achmatowicz rearrangement. Optimization of continuous flow Achmatowicz reactiona. Supporting Information Supporting Information File 133: Experimental section and NMR spectra. Supporting Information File 134: Video of the

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

• ], and reaction conditions optimization [13]. These techniques have also been integrated with robotic platforms to speed up the discovery and synthesis of new materials and drug candidates, showcasing the potential and promising benefits of self-driving chemistry labs [19]. Raghavan et al. [20] compared

• , such as substrate concentrations, bases, and additives, are considered in local models. The development of these models usually involves using HTE [22][23][24] for efficient data collection, coupled with Bayesian optimization (BO) [25] for searching the best reaction conditions to achieve the desired

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• (Scheme 1c). Results and Discussion Optimization To test our hypothesis of using HFIP as a potent solvent in resorcin[n]arene synthesis, initial experiments were conducted using resorcinol and valeraldehyde (Table 1). To compare, Cram’s seminal report from 1989 [9] described the following conditions and

• . bGram-scale reaction (1.10 g of resorcinol). cReaction time increased to 24 h. dAll reactions were performed at 50 °C. Optimization of resorcin[n]arene synthesis using HFIP.a Supporting Information Supporting Information File 124: Experimental procedures for reactions, and relevant spectra of all new

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

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• . Optimized structures are shown for the cyclization transition states (hydrogen atoms are omitted for clarity and bond lengths are given in Å). Scope of cyclization reaction. Reactions of di- and trisubstituted alkene substrates. Optimization of cyclization reaction. Supporting Information Supporting

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• 2 were recognized as versatile building blocks for the construction of 2-amino-3-hydroxypropanoates with 2,3-anti stereochemistry, if appropriate amines work nicely in a nucleophilic manner [44]. After the brief optimization of the conditions for the reaction of 2b and p-anisidine, good yields with

• successful employment of amines as nucleophiles for the epoxy ring opening in a highly stereoselective fashion, we next turned our attention to thiols. Optimization of the reaction conditions based on the ones for amines clarified the tendency that the longer reaction time and the higher temperature

• of the product (Table 4, entry 15). During this optimization process, the obtained product was uncovered not to be a single component but a mixture of two compounds, anti,syn-7a and anti,syn-7b, the latter of which seemed to be produced from the former by the attack of the ethoxide ion released

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

• understanding of the nitrification mechanism and optimization of the reaction. Luo et al. have carried out extensive research on this topic and obtained accurate kinetic data for the nitration of chlorobenzene [17], o-nitrotoluene [18], and p-nitrotoluene [19] by constructing a homogeneous continuous flow

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• abstractions, e.g. to activate gold chloride complexes [18][19]. Therefore, besides the development of new bidentate catalyst motifs, we were still interested in the optimization of these “simpler” derivatives. Thus, we designed a new catalyst motif [20] featuring an isoxazole ring, XB donor 7Z, and compared

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• ). NO release data. Tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamides containing an amino functionality. Synthesis of target furoxanotriazinones 1a–h. The synthesis of furazanotriazinones 7a–h. Control experiment with Na15NO2. Optimization of the diazotization of amide 2aa

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• might be to obtain the pathologically relevant protein targets or off-targets, this may further lead to optimization of the NP scaffold to improve the desired activity. In this review, we focus on the most frequently used chemical proteomic strategies that necessitate a covalent bond between a target

• dozens of kilodaltons. The main advantage of the gel shift assay is to obtain quantitative information of the protein’s probe modification extent, considering high efficiency of the click reaction. Given the bulkiness of the PEG–azide linker, the bioorthogonal reaction needs some optimization, including

• modified peptides can be used for side identification given the relatively high abundance and ionization efficiency due to remaining lysine. The use of the AzTB linker is practical for swift optimization of enrichment workflows, because after the probe–protein conjugates enrichment on the streptavidin