Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• radical activation, resulting in milder and safer reaction conditions [14][15][16]. Given the toxicity of tin-based compounds, there has been significant interest in developing alternative halogen-atom-transfer reagents. Borane, alkylamine, and silane compounds have emerged as effective XAT reagents upon

• photocatalytic activation (Figure 1b) [17][18][19][20][21]. A photocatalytic HAT or SET generates the corresponding boryl, α-amino or silyl radical, which can abstract a halogen atom from alkyl halides to form the corresponding alkyl radical. However, the use of TTMS as a XAT reagent had already been established

• concerning benzophenone hydrogen-atom transfer and silane-mediated activation of alkyl bromides to perform a photochemical Giese reaction, methyl 2-(1,3-dioxoisoindolin-2-yl)acrylate (1) and bromocyclohexane (2) were dissolved in CH3CN (0.1 M) together with a stoichiometric amount of tris(trimethylsilyl

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• commercial perfluoroarene chemical blocks and reagents, involving catalyzed C–F-bond activation and cross-coupling reactions, usually requiring precious transition-metal catalysts and tedious synthetic routes [28][29][30][31][32][33][34]. Therefore, low-cost and facile synthetic strategies are desired to

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

• out IEDADA reactions has been a glowing field in recent years [11][12]. In particular, organocatalysis can provide different activation modes to promote enantioselective IEDADA reactions [13][14], based on three strategies (Figure 3): i) LUMO-lowering activation (Brønsted acid catalysis), ii) HOMO

• -raising activation (amine-based catalysis and N-heterocyclic carbenes), and iii) LUMO-lowering and HOMO-raising activation (bifunctional thioureas and squaramides). Due to the ubiquitous nature of non-covalent interactions in organic systems, they can play a decisive role in asymmetric transformations [15

• -derived azadiene by H-bonding. This dual activation promotes a stereoselective addition of 3-chlorooxindole to the azadiene leading to intermediate A. The latter is also activated by the chiral guanidine and undergoes an intramolecular nucleophilic substitution which delivers the product 19b with the

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• situation. Dibenzyl ester 11c was prepared using traditional activation of carboxylic acid 6a, although the yield was only 23%. A higher yield of the branched ester 11d (86%, as a mixture of diastereomers) was obtained by carbene insertion, generated by blue LED irradiation of methyl 2-diazo-2-phenylacetate

• reaction of more branched alcohols failed. Such esters could be prepared from the dicarboxylic acids using traditional activation or OH-insertion reaction of carbenes formed by irradiation of the appropriate diazo compound. Approaches to 2H-azirine-2,2-dicarboxylic acid derivatives. Synthesis of 2H-azirine

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• ]. This synthetic potential has been demonstrated in a range of insertions into polar bonds [17][18][19][20], C−H activation transformations [21][22][23], and geminal difunctionalizations [24][25]. Within the literature, a broad array of classical methods describes the synthesis of sulfoxonium ylides [26

• ° and C–I bond lengths of 2.1 Å (I–CH2CF3) and 3.2 Å. Finally, a 37.8 kcal/mol activation energy between XB-2 and B for path 1 was calculated. On the other hand, path 2 had a much lower Gibbs free energy of activation of 24.3 kcal/mol, where the angle of attack from 1a to 2a’ was found at approximately

• 160° with equal C–I bond lengths of 2.5 Å in the transition state. The significantly lower activation energy allowed us to conclude that the SN2 mechanism was the more favourable pathway. Conclusion In conclusion, we have developed a direct polyfluoroalkylation reaction of sulfoxonium ylides. The

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

• , alternatively, INT1 could be added to another equiv of 1 via TS2 to form INT2. Although formation of 4 is notably more thermodynamically favorable than INT2 (ΔΔG = −9.2 kcal/mol), a small difference in activation free energy is predicted (ΔΔG‡ = −1.4 kcal/mol). This, at least in part, provides an explanation as

• here that the free energy of activation is lower for chlorination, albeit only by 0.4 kcal/mol. This is consistent with the notion that the kinetic preference can be overcome by increasing the concentration of 1 relative to CF3SF4Cl. In the second product-determining step, Cl atom abstraction by INT5

• activation alone. Overall, our results suggest that this alternating polarity matching effect is subtle and subject to mitigation yet can lead to desirable products if employed thoughtfully. Lastly, following our synthetic and computational studies, accessing a CF3SF4-containing [2]staffane in good yield and

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• proposed by the authors (Scheme 3). Activation of the HVI reagent by H-bonding leads to ligand exchange to give an aminofluoro iodonium intermediate A. Cyclisation occurs via nitrogen attack on the alkene to then give aziridinium intermediate B. Subsequent nucleophilic attack by fluoride on the more

• aza-heterocycles were synthesised in good yields. The authors proposed a mechanism for the fluorocyclisation reactions (Scheme 6), which relies on the activation of the fluoro-iodane reagent 12 with the zinc catalyst. The activation enables better orbital overlap to occur with the π bond of the alkene

• on the alkene gave low yields of product. A mechanism was proposed involving the activation of iodosylbenzene 9 with BF3·Et2O to form an HVI intermediate that activates the alkene to form an iodonium species. Intramolecular nucleophilic attack of nitrogen, elimination of PhI and attack by fluoride

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• active groups for a variety of substrates, making their use as supramolecular organocatalysts based on bifunctional activation mechanism (hydrogen-bonding/Lewis basicity) highly promising. At the same time, additional functional groups that are required for the catalysis can be easily installed on the

• acetonitrile, calix[4]pyrrole enhanced its solubility, contributing to its indirect activation. Various control experiments, such as using CuI with and without calix[4]pyrrole and using dipyrromethane as another potential co-catalyst, have confirmed the role of calix[4]pyrrole as a promoter. Recently

• activation of both substrates via hydrogen-bonding interactions. Additionally, these macrocycles showed excellent activity for sulfa-Michael additions, as well as a moderate activity for Henry and aza-Henry reactions. These results are consistent with the observation reported by Senge and co-workers

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• . From these data, the rate constants of the cycloreversion reactions were generated according to first-order kinetics and used to calculate the enthalpy and entropy of activation with the Eyring equation (Table 1, cf. Supporting Information File 1, equation S5). The analyses revealed half-lives of the

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

• the deslipping-based conversion process [46]. Moreover, considering the similar activation entropy values, the faster deslipping of [3]rotaxane was mainly caused by its lower activation enthalpy than that of [2]rotaxane owing to the stabilization effect derived from the inclusion structure formation

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

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

• mechanism by adding 2 equivalents of TEMPO to the reaction mixture. The absence of the desired product indicated the involvement of a radical pathway in the process. The proposed reaction mechanism begins with the activation of eosin Y by visible light from 5 W blue LEDs, transitioning it to its excited

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• lower level as compared to β-33b. For compound β-33b, the mitochondrial properties and cell viability of melanoma (A375) and squamous cell carcinoma cells (A431) of the skin were studied [31]. Glucoside β-33b resulted in a decrease of the cell viability. In addition, activation of caspases-3 and -7 and

• negative feed-back loop by TRAIL and an upregulation of both receptors. In addition, a loss of mitochondrial membrane potential and release of cytochrome c was observed which gave rise to an activation of intrinsic apoptosis pathways. The mitochondrial response seems to be related to an upregulation of Bax

• in case of compound E-β-46b, the signaling cascade was investigated also for derivative E-β-46e. Important biochemical steps were again activation of caspase-3, downregulation of XIAP, upregulation of p53 and TRAIL receptor 2, STAT-3 dephosphorylation, and loss of mitochondrial membrane potential

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

• reacts with butyllithium, ring closure occurs between the ethynyl and carbamoyl groups, yielding 2,5-disubstituted oxazole-4-carboxylates. This cyclization also occurs when the propargylamine is heated with ammonium acetate, resulting in double activation. Keywords: acid amide; diethyl mesoxalate; N

• -position is hydrolyzed to afford lithium carboxylate 7. In this step, the counter metal ion is considered to affect the activation of the ethoxycarbonyl group of 6. When the reaction mixture was warmed without the addition of acetic acid, a color change to black was observed, suggesting that

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

• and 7a are formed (Scheme 4). Although intermediate 7a has a lower activation energy (∆G = −0.23 kcal/mol), further recyclization processes are not possible due to the positive free energy change (∆G > 0). In this context, the formation of the final product is only possible to proceed via intermediate

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

• transition state is not stabilized, leading to the increase of the activation energy of the reaction. As a result, the reaction does not proceed smoothly. The absolute configurations of product (S)-23c, (S)-23d, and (S)-23e were determined on the basis of their X-ray crystallographic analyses. The validity

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

• . These limitations suggest that a more viable approach to employing FLPs as catalysts for CO2-related reactions could involve their use in CO2 activation [7][18][19]. In particular, the capture of CO2 by FLPs enhances the electrophilicity of the CO2 carbon atom and the nucleophilicity of one of the CO2

• than the catalysts at the top show lower catalytic activity due to insufficient activation of the substrate (Figure 1A, green points). Conversely, catalysts that bind too strongly impede the detachment of the catalyst–reactant complex, thereby reducing the catalyst turnover (Figure 1A, pink points) [26

• ][27]. The previous plots are effective for metal-based catalysts and relatively simple catalytic reactions; however, they fall short when reactions involve multiple steps and independent activation barriers. In this paper, instead of focusing solely on the activation energy, the energy span of the

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

• . Additionally, the π-conjugation system facilitates the redistribution of electron density within the reaction complex, thereby lowering the activation barrier of the reaction [21]. The study employed the following oxidation catalysts for phthalocyanines – PcCo, PcFe(II), PcFe(III), PcMn, PcNi, and PcZn. The

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

• with halogen or triflate groups. Recently, transition-metal-catalyzed direct borylation of arenes via C–H bond activation has been reported, although the design of the substrate and ligands is somewhat complicated [16][17][18][19][20][21][22]. Since the complete removal of catalyst-derived metal

• , 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

• of photocatalysts or UV light irradiation without metal catalysts [45][46][47][48]. Similar homolysis by electrolysis has also been reported [49]. These two activation methods required special equipment (i.e., light sources or electronic devices). To achieve thermal homolysis of the Ar–Bi bonds, the

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

• direct activation of C(sp3)–H bonds under mild conditions [17]. The pronounced electron-deficient W2C nanocatalysts greatly facilitate the direct deprotonation process, ensuring the longevity of the electrode by overcoming self-oxidation. The LSF of drug molecules such as ibuprofen methyl ester and

• derived from the interaction of non-activated alkenes with thianthrene [24]. This procedure has the advantage of separating the oxidative activation of the alkenes from the aziridination step, allowing efficient access to a variety of aziridine building blocks containing sensitive functional groups. This

• carboxylate substrate and [Ru(p-cymene)Cl2]2. Subsequently, the Ru complex coordinates with the aniline substrate, followed by C–H activation to form a six-membered Ru species. The final product is generated through reductive elimination, releasing Ru(0), which is then reoxidized on the anode to regenerate

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

• extensive effort. This involves complex parameter optimization, meticulous validation against experimental data, and careful consideration of diverse reaction conditions and possible reaction mechanisms [28][29]. Although some studies employ transition-state (TS) theory to simulate activation energies and

• compute reaction enthalpy for particular types of reactions [30], this approach often demands significant computational resources to determine accurate TSs and activation energies. The complexity increases further when considering the impacts of solvents and catalysts, which means that large-scale

• ]. Most of the existing methods were originally designed for predicting reaction properties (such as activation energy, reaction enthalpy, etc.) or classifying reactions, but they can be potentially adapted for reaction conditions prediction by modifying the output layer of the model. Both global reaction

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

• -cyclization onto the alkene when n = 3, we modelled this reaction using DFT calculations (Scheme 2). Similarly, we concluded that the present reaction commences with activation of the olefin in 3a by the hypervalent iodine species 8, which is generated under the reaction conditions. The activation occurs via

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose (5) readily accessible form levoglucosan (1, Scheme 1) [24]. Activation of the C4 hydroxy group as triflate and direct treatment with a nucleophilic halogen furnished intermediates 8–11. The latter compounds proved to be difficult to purify

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

• resulting from the substitution of the CF3O group by the trifluoroacetoxy group was then observed. The activation of a fluorine atom from the CF3O group by H+ could be envisaged, which would then trigger the selenium attack to release difluorophosgene and HF, thus generating an episelenonium, which would

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

• modeling of this reaction was performed based on the theory of NO2+ attack, with the activation energy and pre-exponential factor determined. Finally, based on the response surface generated by the kinetic model, the reaction was optimized with a conversion of 87.4% under a sulfuric acid mass fraction of

• values of k0 at different temperatures, the activation energy for the electrophilic attack of NO2+ on the IO can be calculated by the Arrhenius equation: where R is the molar gas constant and T denotes the temperature in Kelvin, and Ea and A are the activation energy and pre-exponential factors for the

• temperatures on the apparent rate constants can be understood. In addition, a complete kinetic model of IO nitration based on NO2+ was developed to describe the reaction process, the activation energy of the IO nitration was calculated to be 192.57 kJ/mol. Furthermore, the accuracy of the kinetic model was