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

• when a minimal quantity of water was used as a solvent in the presence of a base. The ball-milling method efficiently simplified the reaction process because, in contrast to typical solution methods, it may realize product formation without being affected by the solubility of the substrate and other

• reaction that results in the formation of diaryl ethers. Diaryl ethers are important structural motifs in pharmaceuticals and agrochemicals due to their diverse biological activities. Since the 1950s, one of the most used methods for the synthesis of diaryl ethers involves the reaction of phenol with

• diaryliodonium salts. Recent advancements in this field have focused on the development of practically simple and scalable methods for the arylation of oxygen using diaryliodonium salts. By modifying the counter anions attached to the iodonium ion, the stability and reactivity of new symmetrical and

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

• corresponding sulfur-containing heteroarenes, only a few methods have been developed (Scheme 1). In 1988, Lee and co-workers reported the synthesis of SR-containing hydrazones in a two-step process (chlorination [65] then reaction with thiols) from readily available aldehyde-derived hydrazones [66]. Wang et al

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

• /benzoxazepine/benzothiazepine is very important. Due to the wide applications of pyrrole-fused heterocycles, very diverse approaches have been developed for their synthesis [28][29][30][31][32]. In recent years, multicomponent reactions (MCRs) have emerged as one of the most efficient and powerful methods to

• QS (quinine sulfate) (a); emission for 4a, 6c and QS (b); c = 75 ppm in ethanol and T = 298 K. Methods for the construction of pyrrole-fused heterocycles through I-MCR reactions. The model reaction of dibenzoxazepine, gem-diactivated olefin (2-benzylidenemalononitrile), and cyclohexyl isocyanide

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

• ] because of their easily modifiable dipeptide frameworks. Several methods exist for accessing PCPAs, such as the amination of 1-halo-1-alkynes [16][17], tandem reactions of α-imino esters with nucleophiles and electrophiles [18], and the nucleophilic addition of an acetylide to α-carbonylated N-acylimines

• various nucleophiles. This is because the imino carbon atom of 2 is also highly electrophilic, similar to DEMO [23][24][25]. This method offers an advantage over conventional methods as the N-acyl group can be modified by altering the acid amide. In this study, lithium acetylides were employed as

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• : chemosensor; hydrogen sulfide; lanthanide; luminescence; terbium; Introduction The field of luminescent lanthanide chemosensors is rapidly evolving, driven by the need for more efficient, sensitive, and versatile detection methods for environmentally and biologically relevant analytes. While significant

• advances have been made, there remain critical challenges and unmet needs that call for innovative approaches. One of the key motivations for this exploration is the increasing complexity and diversity of analytes that require detection in real-world scenarios. Traditional methods, while effective, often

• fluorescent-based sensors; notable features include large Stokes shifts, extended luminescent lifetimes, and precisely defined emission bands [15]. Typically lasting in the order of milliseconds, their extended luminescent lifetimes enable the implementation of time-gated detection methods, effectively

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• ]pyrimidines using readily available derivatives of azaheterocycles as starting materials. As the last ones, we chose the reaction between 2-aminoimidazole and N-arylitaconimides or N-substituted maleimides, which can be analyzed by both classical synthetic and quantum DFT methods. The second problem solved in

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

• ] and almost planar [19] dodecasubstituted porphyrins have been reported. Despite the increasing interest in the chemical and physical properties of nonplanar porphyrins only limited synthetic methods are available for the functionalization of these macrocycles [6]. An attractive approach to accomplish

• , even with Ni(II) metalation. There are many other methods available to achieve different desired atropisomeric ratios. These include thermal enrichment [67][68], photoracemization [69][70], axial-ligand coordination [71], precise separation techniques [50] or a combination of the procedures mentioned

• [72]. Many more examples of atropisomeric enrichment methods can be found in a 2024 review on atropisomerism by Maguire et al. [73] and could be further explored to isolate the αβαβ-atropisomer of porphyrin 11. X-ray crystal structure analysis of compound 37 Interestingly the anthracenyl arm-extension

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• a tetrafluoroethylene group on an asymmetric carbon center. In order to overcome the current lack of synthetic methods for preparing such molecules, we came up with the idea of utilizing the [1,3]-proton shift reaction reported by Soloshonok et al. In 1997, Soloshonok et al. reported that

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

• -indolenines, specially the spiro-heterocyclic indolenines, can be considered as a privileged scaffold, present in several natural products with interesting biological activities, as depicted in Figure 1 [4][5][6][7]. Among the known methods of synthesizing spiro-heterocyclic indolenines, the dearomative

• efficient methods for the synthesis of heterocycles by multicomponent processes and domino reactions [16][17][18][19][20], here we disclosed the oxidative one-pot four-step synthesis of 2-amino-3,3’-spiroindolenines using readily available tertiary amines, electron-rich anilines and isocyanides as starting

• laboratory, and the results will be reported in due course. Experimental General methods 1H, 13C and 19F NMR spectra were recorded on a JEOL 400 spectrometer (at 400 MHz, 101 MHz and 376 MHz, respectively). Unless otherwise stated, NMR spectra were recorded using residual solvent as the internal standard; 1H

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• . Their privileged structures have led organic and bioorganic chemists to develop methods to construct them. Our fundamental knowledge in enzymology is continually expanded by enzymes involved in natural products biosynthesis, as their production requires evolved enzymes to perform chemical reactions

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

• ][19][20]. Consequently, in recent years, new methods have been developed to introduce various functional groups at position 5 or 6 of uracil [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. However, only a few methods are

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

• Yukiko Karuo Keita Hirata Atsushi Tarui Kazuyuki Sato Kentaro Kawai Masaaki Omote Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan 10.3762/bjoc.20.226 Abstract In this study, we develop the synthesis methods of fluoroalkenes and

• synthetic methods for fluoroalkenes have attracted considerably and become increasingly necessary in pharmaceutical and industrial fields. Fluoroalkenes have been constructed in a variety of methods [4][5][6][7][8][9][10][11][12][13][14], and one of the methods is to make use of fluorine-containing building

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• centres are indicative of the FLP’s reactivity [45][46]. Thus, substituents must be selected to ensure a broad spectrum of acidity and basicity of the LA and LB. Different methods for determining these properties have been described in the literature. Because of their easy computation, the proton affinity

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

• very weak estrogenic activity [8]. Although a detailed SAR is still warranted, the initial reports prompted us to find a suitable synthetic method for 5-substituted 2-hydroxybenzopheneones, and to evaluate their UV-absorbing properties. Various methods for the synthesis of benzophenones have been

• -hydroxybenzophenones are conventionally prepared via Fries rearrangement of a phenyl ester [10]. Organocatalytic methods have also been reported for the synthesis of 2-hydroxybenzophenones [11]. In addition, several metal-mediated methods for their synthesis have been reported. For example, the Rh-catalyzed

• environmental hazards, and this can only be circumvented using a transition-metal-free synthesis protocol. Although eco-friendly methods for the synthesis of 2-hydroxybenzophenones have been reported via a cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water [15], an alternate and more

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ) were observed with similar mass spectra. The amount of secretion available and the complex mixture did not allow for the isolation of enough material for NMR analysis. Therefore, for the structure elucidation of these unknown compounds, we used different analytical methods, including GC–MS, GC–IR, and

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

• properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some

• substituted/modified CDs. Recent studies combining experimental methods with molecular modeling have revealed that the maximum number of water molecules entrapped inside the macrocyclic cavity is 6 for α-CD [13] and 10 for β-CD [14]. Notably, the exact number of the encapsulated water molecules by γ-CD and

• upon heating. Conclusion Using experimental and computational methods as well as available literature data, the present study reliably estimates the number of water molecules present in γ-CD, their preferable binding position, and thermal stability. Comparison with the other cyclodextrins revealed that

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• that the hierarchal molecular self-assembly of these materials into larger structures directly influences behaviours such as performance and stability. It is therefore imperative that these materials are characterised effectively over multiple length scales. Two effective methods of achieving this are

• , characterisation techniques, and applications of molecular gels; which still remains deeply insightful despite the rapid advancement of the field [10]. A more recent review by Yu et al. summarised a number of techniques used to characterise supramolecular materials [11]. Two of the most commonly used methods of

• from being achieved. In this review, we aim to highlight and discuss a number of strengths and limitations provided by these techniques and will show how using these characterisation methods to complement each other can provide a much better understanding of self-assembling systems. Review Imaging

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• -hydroxy-6-methyluracil, etc.). One of the successful methods for hydroxylation is peroxydisulfate oxidation. By modifying the Elbs reaction through catalysis and the introduction of additional oxidants, we have been able to significantly increase the yields of practically useful compounds. Keywords

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

• under transition-metal-free and open-air conditions. Conventional methods required photoirradiation or electrolysis to generate aryl radicals from triarylbismuthines. In this study, it was found that simply heating the solution of triarylbismuthines in benzotrifluoride (BTF) in air successfully led to

• , the development of new synthetic methods of arylboronates using stable and versatile reagents under transition-metal-free conditions has recently attracted much attention [23][24][25][26][27]. In particular, the use of radical reactions has been considered as one of the effective methods, since

• , and their derivatives can be easily synthesized by common Grignard reactions [37][38][39][40][41][42][43][44]. Three activation methods have been reported for their use as aryl radical sources. It has been reported that the homolysis of Ar–Bi bonds could be achieved by photoirradiation in the presence

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

• , 52074, Aachen, Germany 10.3762/bjoc.20.214 Abstract With the resurgence of electrosynthesis in organic chemistry, there is a significant increase in the number of routes available for late-stage functionalization (LSF) of drugs. Electrosynthetic methods, which obviate the need for hazardous chemical

• gaining increasing interest in both academia and industry due to its numerous advantages and potential applications [1][2]. Electrochemical methods can reduce costs and waste generation by eliminating the need for chemical oxidants or reductants, and they can be safely and easily scaled up in flow

• achieved compared to many classical methods. In light of the general trend towards more chemoselective protocols with broader functional group compatibility, there has been a growing interest in exploring the potential of electrosynthesis for the late-stage functionalization of complex scaffolds

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

• transformations, then reaction extraction and separation, into a single process, which are typically performed individually/separately in batch methods. This enhances the overall efficiency for obtaining the desired product(s) from the reaction mixture. In continuation to our efforts on developing flow-based

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

• aspects of the dataset features and data preprocessing methods. Moreover, we introduce common algorithms and representative studies for developing both global and local models. We highlight representative studies that demonstrate the effectiveness and applicability of these algorithms in real-world

• scarcity and diversity, as they need to cover a vast reaction space [26][27]. However, collecting data relevant to chemical reactions represents a significant challenge. While specific molecular properties can be precisely computed using existing simulation methods like quantum chemical calculations

• theoretical calculations are typically restricted to gas-phase reactions [31]. Despite these challenges, recent advances in quantum chemical methods have shown that theoretical calculations can provide practical guidance for validating experimental results [32]. Thus, we posit that the role of theoretical

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

• well known as a potent β-lactamase inhibitor [33][34]. It is produced by the filamentous bacterium Streptomyces clavuligerus, but in low yield. Various clavams 2–5 have been identified (Figure 2B), either through isolation as natural metabolites or obtained by synthetic methods [35][36][37][38][39][40

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

• many organocatalysts [3][4][5], natural products (e.g., the potent α-glucosidase inhibitor (−)-codonopsinol B) [6][7], and pharmaceutical drug molecules such as saxagliptin and ramipril (Figure 1) [8]. Accordingly, the development of methods to access substituted prolines and pyrrolidines is an

• important area of study as this ring system is prevalent in many useful molecules. Typical literature procedures include multistep derivations of proline itself, e.g., the destruction of the stereocenter and then its reinstallation by an enantioselective conjugate addition [9]. Other methods include the

• enantioselective conjugate addition to α,β-unsaturated pyroglutamic acid derivatives followed by deoxygenation [10], and the enantioselective organocatalytic reaction between 2-acylaminomalonates and α,β-unsaturated aldehydes [11][12]. The development of new synthetic methods using hypervalent iodine reagents has

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• interests, no methods have been described to synthesize both trifluoromethoxylated and phenylselenylated molecules. The introduction of a CF3O moiety into organic molecules remains poorly described in the literature, especially the direct trifluoromethoxylation [44][45][46]. Only few radical

• trifluoromethoxylations of (hetero)aromatics [47][48][49][50][51][52], enol carbonates [53] or silyl enol ethers and allyl silanes [54] have been reported. Most of the methods described have used the trifluoromethoxide anion (CF3O−) [45]. Many sources of the CF3O− anion have been described, but with certain drawbacks