Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• in the reaction with a diphenylpicrylhydrazyl (DPPH) radical, ABTS·+ radical cation, CUPRAC test, and inhibition process of superoxide radical anion formation by xanthine oxidase (NBT assay). The presence of a catechol fragment and thioether or thione groups determines the ability to neutralize

• fragment favors the pronounced antiradical activity. The use of ABTS radical cation to assess the antioxidant capacity of compounds is one of the widely used methods which is based on the transfer of an electron from the studied molecules to the acceptor [67]. The obtained IC50 values for synthesized

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

• formed in this process abstracts the γ-CH proton of the CF3-imine (136 → 141), facilitating its nucleophilic attack on the isatin cation (141 + 142 → 143), followed by elimination of the catalyst 138, which completes the cycle liberating 139 (Scheme 29). Overall, this methodology represents a convenient

• ]-rearrangement of ene-aldimines 149, catalysed by the BINOL-derived chiral phosphoric acid (CPA) (R)-151 (Scheme 31) [46]. DFT computational analysis suggested that the reaction proceeds via a complex cascade that involves the fragmentation of ene-aldimine 149 to form an imine methylene cation, which in turn

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• [D3]-formamide. The ability to deuterate at benzylic positions is particularly relevant as benzylic C–H bonds are common in biologically relevant chemotypes and moreover appear in approximately 25% of the top selling 200 pharmaceuticals [23]. Benzyl cation stability is a driver of metabolism at these

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• . Keywords: anthracene; cation; dimerization; radical; reactivity; Introduction Organic radicals have garnered significant attention in various research fields, including catalysis [1][2][3][4], chromophores [5][6][7][8], and as agents in dynamic nuclear polarization [9][10][11][12]. Recently, highly stable

• O–O bond cleavage to give compounds 1 and 5 (Scheme 2). Owing to the high reactivity of the DAntM radical, cyclic voltammogram (CV) was measured by using the stable DAntM cation, prepared from compound 3 oxidized by antimony(V) chloride, which can be characterized by 1H, 13C NMR, and UV–vis

• spectroscopy under ambient conditions. The CV of DAntM species showed a reversible wave at E1/2 = −0.20 V (V vs Fc/Fc+) (Figure 5a) [39]. This redox potential is close to that of TAntM radical and cation [17]. Additionally, at a scan rate of 0.1 V s−1, the current peak intensity on the anodic side (from

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• Chatani et al. reported that a carbon radical generated by the reaction of RB(OH)2 with Mn(acac)3, added to isocyano groups, is leading to intramolecular cyclization with an ortho-aryl group. The formed aryl radical is oxidized by Mn(acac)3 to convert into an aryl cation, which can be deprotonated to

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• substrates also increase yields. The ionic liquid [bmim][InCl4] can be used as a catalyst for the one-pot synthesis of pyrazoles 68 from 1,3-diketones, aldehydes, and hydrazines (Scheme 23) [101]. The synergistic effect between anion and cation favors high regioselectivity, and high yields can be observed in

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• formation of dimeric side products. Cyclic voltammetry analysis suggested an initial anodic single electron transfer (SET) to radical cation 5, cyclization and deprotonation. Subsequent SET oxidation in solution by 5 led to cation 7. Final deprotonation furnished aromatic cycle 4. In 2022, Zhang et al

• the electrolysis was a four-electron oxidative process. Based on this study, the authors proposed the initial anodic oxidation of hydrazone 44 through the loss of two electrons and one proton to form cation 47. Subsequent nucleophilic addition of the azaarene led to new highly acidic cationic species

• species to be oxidized, initial SET anodic oxidation of the hydrazone furnishes the highly electrophilic radical cation species D, which undergo nucleophilic addition of the second partner and deprotonation to produce hydrazinyl radical F (route a). Alternatively, if the partner possesses a lower

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• , initiating further radical reactions through the formation of radical cations B. Nucleophilic arylmethyl radicals C, which are generated from radical cations B by desilylation, undergo an addition reaction with 2-benzopyrylium intermediates A, giving rise to the corresponding radical cation. Catalytic cycle

• II is completed through a SET from D, a reduced form of the photoredox catalyst 2-benzopyrylium intermediates A, to the generated radical cation, affording 1H-isochromene derivatives 3. The photoredox cycle is also completed with the regeneration of cations A through SET from D. The most distinctive

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• similar to 6. They observed high N1-selectivity using NaH in THF with pentyl bromide and electron-deficient indazoles, postulating a coordination of the indazole N2-atom and an electron-rich oxygen atom in a C-3 substituent with the Na+ cation from NaH. Under anhydrous conditions the yields ranged from 44

• -3 as a bidentate ligand to the Na+ cation from NaH. The tight ion pair would direct alkylation under conditions A to N1. As this and other postulations exist, we explored the possible mechanisms of each reaction conditions computationally. All calculations were performed in implicit THF at the

• subsequently set to 0 kcal/mol leading to the energy diagram in Figure 5. Two TSs leading to each product were found, all four of which utilized a coordinating Cs+ cation. The N1-s-cis and N1-s-trans TSs were the lowest in energy (27.5 kcal/mol and 29.1 kcal/mol, respectively), leading to two conformations of

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• amount (5%) of the N,N’-diaryldihydrophenazine radical cation that is the byproduct corresponding to the intermolecular oxidative C–N coupling of the diarylamine A1 was detected in the reaction mixture. This emphasizes that the both processes are of the same nature and proceed through the same

• intermediate (i.e., the diarylamines’ radical cation) and indicates the dominance of the intramolecular cyclization over the intermolecular C–N coupling process. Oxidation of diarylamines in the presence of an excess of trifluoroacetic acid gave no targeted pyridoindazolium salts, whereas the amount of

• A1, similarly to the chemical oxidation. The radical cation of dihydrophenazine formed was isolated and studied using ESR and HRMS methods. The ESR spectrum (see Supporting Information File 1) was typical for this type of compounds: a characteristic quintet due to hyperfine splitting on two

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• cations that offer unique reactivities as intermediates in various bond-formation processes. Such intermediates can potentially take part in both radical and ionic bond formation; however, the mechanisms involved are complicated and not fully understood. Herein, we report electrochemical radical cation

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• representative radical cation precursors that are widely used to realize the formation of unique bonds. The respective radical cations are trapped by various nucleophiles under radical and/or ion control, where kinetic and/or thermodynamic effects are expected to be dominant. Typical examples that clearly show

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• . prepared the Brønsted acid ionic liquid 7, based on the 1-(butyl-4-sulfonic)-3-methylimidazolium cation, (Scheme 4) and tested it in the model reaction reported in Scheme 2 (R = t-Bu), obtaining a 71% yield using 20 mol % of catalyst in ethanol as the solvent under reflux conditions. The yield could be

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• trap the phenoxonium cation formed in the oxidation as an acetal, that later were hydrolysed to the quinone. Formation of hydrogen gas as the cathode reaction caused challenges in the flow cell and were overcome by recycling the reaction mixture through the cell at increased flow rate several times

• chrysenols nor phenanthrols, suggesting a chemically irreversible reaction of the radical cation intermediate with the ensuing product no longer being electrochemically active within the potential window of the CV scans. However, a reduction peak was observed for compound 1b (see Figure S2 in Supporting

• radical and a naphthyloxy cation leading to the formation of 5. Our CV studies exhibit oxidation peaks, which seem in line with what to expect for an electrochemical oxidation of PAPs. Through the cyclic voltammetry experiments for the investigation of the redox behavior of the PAPs, an estimation of

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from

• interactions [4]. Protonation of 3-fluoropyrrolidine generates the 3-fluoropyrrolidinium cation, and this typically results in a highly favored conformation in both the gas phase and solution where the fluorine and nitrogen atoms are cis, mirroring the behavior observed in analagous 4- and 6-membered ring

• -fluoropyrrolidine. To investigate potential changes in the preferred orientation of the fluorine substituent in 3-fluoropyrrolidine and the respective cation, an additional fluorine atom was introduced into the molecule for theoretic studies (Figure 2). The subsequent evaluation focused on the role of anomeric and

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• functional groups on the aromatic ring and adjacent to the benzylic position. Mechanistic investigations suggested an initial electron transfer to generate a radical cation en route to the intermediate benzylic radical, rather than a HAT process, however, the authors did not distinguish between a stepwise

• a potent HAT reagent capable of generating the benzylic radical, which then performs FAT with Selectfluor to generate the desired benzyl fluoride. Alternatively, the benzylic radical could further be oxidized to the cation, and in the process, regenerating the ground-state catalyst. The benzylic

• cation would then be trapped by the previously liberated fluoride. This reactivity was demonstrated on one primary, one tertiary and eight secondary substrates. When diphenylmethane substrates were subjected to the reaction conditions benzylic ketone products were observed. As highlighted by the examples

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• -deficient alkynes [59][60][61][62][63]. The in situ generated cyclic intermediate C has a resonance hybrid C’. Then, the further nucleophilic addition of the electron-rich enamino unit to 5-(alkylimino)cyclopenta-1,3-diene intermediate C gave intermediate D. At last, the coupling of the iminium cation with

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• (halogen or hypervalent bond) between chloride anion and diarylchloronium cation 9 is non-covalent and likely dominated by electrostatic attraction. A similar switch from non-covalent halogen bond for the lighter (X = Cl and Br) to partially covalent halogen bond for the heavier (X = I and At) was also

• (mesityl)iodonium cation (3) the iodine atom uses 88.54% p-character to bond with the phenyl group. Phenyl iodide (27) has three lone-pairs, whereas the phenyl(mesityl)iodonium cation (3) has two lone-pairs (though it does have another aryl group), and therefore this observation is consistent with Bent’s

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• product of monomer 6. The proposed mechanism is shown in Scheme 2. Anodic oxidation of thioglycoside 6 generated radical cation 11, which was converted to glycosyl triflate 12. 1,6-Anhydrosugar 7 was produced via 4C1-to-1C4 conformational change of the pyran ring to generate cation intermediate 13

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• -hydrazino form [17][24][25], we conceived the idea of reversing the reactivity of 4a–r in the six-membered cyclization process (N- vs O-annulation) through the generation of an electrophilic oxocarbenium [26][27] cation intermediate from the acetal residue at N-3 of the (thio)hydantoin core. To pursue our

• providing intermediate A. The latter, by loss of a trichloro(alkoxy)ferrate(III) anion, generates a strong electrophile such as the oxocarbenium cation intermediate B. The released trichloro(alkoxy)ferrate(III) splits into FeCl3, which enters the catalytic cycle, and a free alkoxide, which acts as a base

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• in the appropriate vicinity for the reaction to take place in appreciably good yields (84%). The barium cation template is the key for the reaction, as is the base concentration for effective hydride transfer (Scheme 14) [29]. They also extended the scope of the intramolecular Cannizzaro reaction to

• proposed strategy where the metal ion acts as the binding cation template for the intramolecular desymmetrization (Scheme 15) [82]. A similar highly efficient intramolecular Cannizzaro reaction of calix[4]arene dialdehydes was observed by Galli et al. where the 1,3-distal cone 35 significantly responded to

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• iridium photocatalyst [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 leads to excited-state *[Ir(III)], Ered (*[Ir(III)]/[Ir(II)]) = +1.21 V, possessing sufficient energy to oxidize PPh3, forming the triphenylphosphine radical cation. Subsequently, benzoic acid undergoes deprotonation facilitated by a base, producing

• benzoate. This benzoate then reacts with the triphenylphosphine radical cation, resulting in the formation of the phosphoranyl radical intermediate, which undergoes β-scission, leading to the formation of a benzoyl radical, accompanied by the liberation of a triphenylphosphine oxide molecule. After this

• salicylic acid derivatives and aryl acetylenes. Due to irradiation with blue light, Mes–Acr–Me+ gets excited to Mes–Acr–Me+* and takes up a single electron from Ph2S. The reaction of the diphenyl sulfide radical cation with carboxylate and successive acyloxy C–O bond cleavage forms diphenyl sulfoxide and an

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

• hyperconjugation via bending the exocyclic methyl group such that the formal p-orbital at C3 no longer aligns with the C2–C7 bond results in the 6/6/6-tricyclic C3 tertiary cation B2+, which is 13.0 kcal mol−1 higher in energy. In principle, either A2+ or B2+ could be deprotonated to form products. A similar

• 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

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• heterocyclic compounds [20][21][22]. Particularly dialkyl bromoketones have been utilized in natural product synthesis [23][24][25], also as a precursor to reactive oxyallyl cation intermediates [26][27][28], and for their photochemical reactions [29]. However, the direct halogenation of unsymmetrical ketones

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• . With an electrochemical window of up to 6.3 V, which is unprecedented for TAAILs with an NTf2 anion, this new class of TAAILs demonstrates the opportunities that arise from modifications in the backbone of the imidazolium cation. Keywords: conductivity; electrochemical window; ionic liquids; tunable

• use in different fields of chemistry like synthesis [4][5][6][7][8][9], catalysis [10][11][12][13][14] and materials science [15][16][17][18][19][20][21][22][23]. ILs generally consist of an organic cation [24], such as the imidazolium or ammonium ion and an inorganic anion like a halide anion or

• introduced a new class of ionic liquids based on the 1-aryl-3-alkylimidazolium cation in 2009, the tunable aryl alkyl ionic liquids (TAAILs) [29]. This class of ionic liquids allows the modification of physical and chemical properties by variation of the functional groups present at the aryl ring of the

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• improving their thermal stability, and more specifically, of designing evaporable fullerene derivatives [16][17][18]. Recently, we reported on perovskite solar cells fabricated with indano[60]fullerene ketone (FIDO), which was synthesized through fullerene cation chemistry. These cells demonstrated long

• fullerene cation chemistry as reported by our group [20][21][22][23][24][25][26]. Conversion from ketone to thioketone is usually achieved by using Lawesson's reagent, which tends to form a trimer structure when reacted with indanone without a substituent at the α position [27][28][29]. Introduction of