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

• chains and derived from the classical triphenylene core self-assembling in columnar mesophases based on this paradigm. These mesogenic compounds were simply obtained in good yields by the nucleophilic substitution (SNFAr) of various types of commercially available fluoroarenes with the electrophilic

• variety of triphenylene derivatives (Figure 1) [44][45][46][47] based on the nucleophilic substitution of various electrophilic perfluoroarenes, including C6F2H4, C6F6, C10F8, and C6F5-Ph, by nucleophilic organolithium reagents. e.g., 2,2’-dilithio-4,4’,5,5’-tetrakis(alkoxy)-1,1’-biphenyls, 2Li-BPn

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

• fluoroalkyliodonium salts as sources of electrophilic trifluoroethyl synthon. Given the non-nucleophilic nature of the iodoarene byproduct, this protocol should not suffer from further reactivity that decomposes the ylide. We describe here the coupling of α-carbonyl sulfoxonium ylides with polyfluoroalkyl(aryl

• discovered by Umemoto has proven an effective electrophilic trifluoroethyl transfer reagent [34][35], and to further explore the potential of fluoroalkyliodonium salts we evaluated the reactivity of such compounds in the context of sulfoxonium ylide derivatization. As depicted in Table 1, we began our

• with them being viable electrophilic sites for halogen bond formation with 1a, supporting the mechanism in path 1. We also expressed the LUMO and LUMO+1 molecular orbitals of 2a’ (Figure 3, middle and right, respectively), which showed lobes centered on the I–C bonds to both the trifluoroethyl and

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• intramolecular SNAr reactions. Ugi-4CR/deprotection/cyclization (UDC) strategy: In the UDC approach a protected amine and an electrophilic functional group like esters or ketones are used. Convertible isocyanides can also be employed. Once the Ugi reaction is completed, the protecting group is removed, and 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

• , the carbon-centered radicals in both INT1 and INT4 are closer to strong electron-withdrawing groups than are the radical centers in INT2 and INT5, rendering INT1 and INT4 relatively more electrophilic. Inductive effects drop off steeply with distance, and it is also established that a substituent (or

• , e.g., a radical or cation) on the transannular carbon atom of a bicyclopentyl moiety can interact through space [35][63][64]. The consequence is ostensibly that more "nucleophilic" INT2 and INT5 are better matched for Cl atom abstraction from the "electrophilic" reagent (SF5Cl or CF3SF4Cl). To test

• -chloropyrimidyl-SF4Cl) was determined to be significantly less "electrophilic" than SF5Cl or CF3SF4Cl, consistent with a reduction in the radical polarity matching effect (see Supporting Information File 1 for details). This was difficult to predict or rationalize based on calculation of free energies of

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

• structures. HVI reagents are characterized by their diverse reactivity as oxidants and electrophilic reagents. In addition, they are inexpensive, non-toxic and considered to be environmentally friendly. An important application of HVI reagents is the synthesis of halogenated cyclic compounds, in particular

• fluoride ion to displace PhI. In pathway B (bottom), the nitrogen is oxidised by the iodane, generating an electrophilic intermediate B. Nucleophilic attack by the double bond subsequently forms the 6-membered ring intermediate C, which is either immediately attacked by fluoride to form both cis and trans

• difluoroiodobenzene 10 is formed in situ, which is activated by HF. Two possible mechanisms were given for the synthesis of pyrrolidines 14, which are the same two proposed for the synthesis of piperidines 6 (Scheme 1). Either an alkene-activated iodonium is formed or an activated electrophilic nitrogen is generated

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

• electrophilic CO2, leading to the formation of 18-IV. The negatively charged oxygen in 18-IV is then responsible for removing the chloride atom leading to the major isomer as a final product. The results of this study suggest that nonplanarity or distortion of the tetrapyrrolic macrocyclic core is not a

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

• alkenes 41 was disclosed (Scheme 17) [59]. The target 6-trifluoromethyl peroxides 42 were synthesized in good yields under mild conditions. The electrophilic CF3 radical A, generated from CF3SO2Na through single-electron oxidation by using Mnn/TBHP system, is captured by the carbon–carbon double bond to

• fragment: In 2016 a radical difunctionalization of styrenes 163 using electrophilic perfluoroalkyl compound 164 and tert-butylperoxy radicals with the formation of (1-(tert-butylperoxy)-2-perfluoroalkyl)ethylbenzene 165 was developed (Scheme 52a) [115]. The proposed mechanism includes the Co(II)/Co(III

• catalytic cycle. A Pd-catalyzed synthesis of di-tert-butylperoxyoxoindole derivatives 210 from acrylic acid anilides 209 and TBHP was developed (Scheme 65) [134]. The authors proposed that the initially formed diperoxide A undergoes electrophilic attack by cationic Pd(II) on an aromatic C–H bond with the

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• concentrated on iodine [19], making it highly electrophilic, while a nonbonding pair of electrons is mainly centred on the axial substituents, causing a build-up of electron density on these positions (Figure 1A) [1][20]. Stabilisation of this charge on the axial substituents by strong electron-withdrawing

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

• unsymmetrical forms of these salts serve as effective electrophilic arylating reagents in various organic syntheses. The use of diaryliodoniums in C–C and carbon–heteroatom bond formations, particularly under metal-free conditions, has further enhanced the popularity of these reagents. In this review, we

• concentrate on various arylation reactions involving carbon and other heteroatoms, encompassing rearrangement reactions in the absence of any metal catalyst, and summarize advancements made in the last five years. Keywords: arylation reaction; diaryliodonium salts; electrophilic arylation reagent; metal-free

• arylation; rearrangement reaction; Introduction The chemistry of hypervalent iodine compounds is well-established and they are prevalent as oxidants and electrophilic reagents in organic conversions [1][2][3]. They have gained significant attention due to their high reactivity and ability to carry out

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

• transformation, experiments with different SCF3 sources were conducted. First, we hypothesized that trifluoromethylthiolated succinimide, which might be in situ generated from NBS and AgSCF3, could be the active species. When the reaction was carried out in the presence of this electrophilic source and 1a, no

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

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

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

• -O-trimethylsilyl-ʟ-rhamnopyranose (4b) with TMSI gave intermediate A containing an anomeric iodide. Electrophilic addition of rhamnosyl iodide A to one of the two imino groups of 13 gave intermediate B. Another electrophilic addition of n-propyl mercaptane to the second imino group afforded

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

• -acylamine; oxazole; propargylamine; Introduction Propargylamine is an important motif in the synthesis of heterocyclic compounds [1][2][3][4] and drug discovery [5][6] due to its multifunctionality, which includes a basic and nucleophilic amino group, an electrophilic and dipolarophilic triple bond, and an

• derivative has been employed (Scheme 1) [13][14]. Recently, we have demonstrated that the central carbonyl group of DEMO is highly electrophilic, facilitating the nucleophilic addition of less reactive reagents such as acid amides [23][24][25][26]. When the reaction was conducted in the presence of acetic

• 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

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

• by these findings, we now explored difluoromethylation reactions with compounds bearing less nucleophilic functional groups. Ketones caught our particular attention as they contain a weak nucleophilic carbonyl oxygen adjacent to an electrophilic carbonyl carbon. Previous studies have focused on

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

• reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine. This compound might undergo an additional visible light-mediated oxidation to furnish a second iminium intermediate, which acts as electrophile in an intramolecular electrophilic

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

• blocks. When using them as nucleophilic reagents [15][16][17][18][19][20], the reaction between anion species, such as fluorine-containing Horner–Wadsworth–Emmons reagents, and carbonyl compounds led to E-selective olefination (Scheme 1A) [15]. On the other hand, some reactions with electrophilic

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

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

• initial study, it can be concluded that the mechanism for our system proceeds according to mechanism two. The following simulations were performed on this conclusion. Regioselectivity PO exhibits two distinct electrophilic sites, which can be subject to nucleophilic attack (Figure 2B). Thus, the

• new intermediate (Min5) is stabilised, in which the oxygen of CO2 has attacked the electrophilic carbon of PO, and the oxygen atom of PO interacts with the LB. This mechanism is exclusive to phosphorus-containing FLPs, as nitrogen does not support this type of reactivity. Subsequently, 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

• not increase the yield of pyridine 11 further (Table 2). Despite the numerous works in the field of peroxydisulfate oxidation, there is still no unified view of the reaction mechanism. Consequently, in [31], the assumption of an electrophilic substitution mechanism for the Elbs and Boyland–Sims

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

• atomoxetine, metaxalone, and tadalafil. Mechanistically, thiophenol is oxidized at the anode to the corresponding radical by SET, then dimerizes into a disulfide, which is further oxidized into an intermediate cation radical, yielding a highly electrophilic species. Subsequently, a selective anisole attack

• =C bond in the Co–alkene complex, forming an intermediate alkyl radical, which is further anodically oxidized to produce an intermediate alkyl cation. Another indole molecule undergoes electrophilic alkylation by this intermediate, forming an indolyl cation, which upon deprotonation yields the final

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

• developed an electrophilic phenylseleno trifluoromethoxylation of alkenes, which leads to β-selenylated trifluoromethoxylated compounds or, upon subsequent reduction, to the trifluoromethoxylated ones. Keywords: DNTFB; electrophilic addition; fluorine; selenium; trifluoromethoxy; Introduction Due to the

• compounds from alkenes and DDPyOCF3, more precisely to α-trifluoromethoxylated, β-phenylselenylated compounds. Results and Discussion The electrophilic addition of phenylselenyl halides to alkenes to form a selenonium intermediate that can be intercepted by an external nucleophile is a well-known method to

• obtain 1,2-disubstituted compounds [72][73][74]. Therefore, the reaction of alkenes with electrophilic sources of phenylselenyl in presence of DDPyOCF3 as a nucleophilic source of the CF3O group was studied (Table 1). First, we started from the optimal conditions previously established for the

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

• 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

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

• in a Mannich reaction [4]. In 2018, our group showed in a proof-of-principle study [5] that the Lewis acid catalysis by DAI salts is based on halogen bonding (XB), an interaction between a Lewis base (XB acceptor) and an electrophilic halogen atom in the Lewis acid (XB donor) [6][7][8][9][10]. In

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• excellent enantioselectivities (89–98% ee) and low to moderate yields (48–72%). The homologation step proceeds via the stereoretentive 1,2-migration of the vinyl group from the tetracoordinated boron to the highly electrophilic carbon of the diazomethane, concerted with the elimination of the nitrogen

• transfer reagents; (iv) direct metal-free imine carbanion addition to electrophilic alkene. Class (i) underwent an evolution from catalysis by covalent interaction to chiral hydrogen-bonded catalysis, which allowed the expansion of the allyl component scope from simple allyl to substituted allyl groups

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

• /off-target protein and a tested NP or a similar active small compound (Figure 1). The covalent bond serving this purpose can be formed in two distinct ways: either the NP or small compound already contains a reactive, often electrophilic group directly or the reactive group, for example a photo

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• general, transition metal catalysts are required to effect efficient NGT to unactivated olefins because iminoiodinanes are insufficiently electrophilic to engage in direct aziridination chemistry. Here, we demonstrate that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) activates N-arylsulfonamide-derived