Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• this case, the mechanism appears to proceed through the formation of free radical species, where APS plays the role of oxidant and radical activator of DMSO, generating reactive radical species of DMSO or dimethyl sulfone that react with the nitrogen of saccharine compound 19 without the need for a

• catalyst. Another recent example for the use of DMSO as C1 synthon was reported by Bhattacharjee et al. They used DMSO in a 3CR to install a methylene unit between an indazole 24 and a carboxylic acid 25 (Scheme 18) [52]. Under radical conditions using K2S2O8, they obtained a series of carboxylic acid

• salts and TEMPO as the radical initiator/oxidant couple that promoted the intramolecular radical cyclization of suitable 1,3-dicarbonyl Ugi adducts 54 and 55 (Scheme 45) [108][109]. The stabilization of the enol in the 1,3-dicarbonyl Ugi adduct allows single-electron transfer (SET) with the anion

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• higher selectivity with milder reaction temperatures. The weaker C(sp2)–Br bond is easier to cleave than a C(sp2)–H bond, resulting in a higher likelihood of radical substitution at those positions. To the best of our knowledge, there are no previous examples of perfluorobenzyl substitution of any PAH(Br

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• benefits of the photomechanochemical approach in the field of synthesis [77]. Specifically, they developed photomechanochemical conditions for the atom-transfer-radical addition (ATRA) of sulfonyl chlorides to alkenes, pinacol coupling of carbonyl compounds, decarboxylative acylation, and photocatalyzed [2

• reactions: A) atom-transfer-radical addition, B) pinacol coupling, C) decarboxylative alkylation, D) [2 + 2] cycloaddition. The photo in Scheme 11 was reproduced from [77] (© 2024 F. Millward et al., published by Wiley-VCH GmbH, distributed under the terms of the Creative Commons Attribution 4.0

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• starts with a single-electron oxidation of 4a on the electrode surface to form cation radical A, in which Br(II) is chelation-stabilized by the carboxyl group [21] and the neighbouring Br substituent [24]. Intermediate A rapidly undergoes irreversible chemical reaction by HFIP coordination to transient

• Br(II) followed by subsequent deprotonation to generate radical B. A following disproportionation of radical B would lead to the formation of Br(III) species C (anodic oxidation cannot be fully excluded), which undergoes intramolecular SNAr-type substitution to form cyclic λ3-bromane 1a and

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• to inhibit p38α MAPK and 0.5 µM for TNF-α [10]. Pyrazolobenzothiazines containing a triazole moiety have also been studied as potential antibacterial drugs [7]. Other applications of N-substituted benzyl/phenyl acetamide pyrazolobenzothiazines include superoxide anion and DPPH radical scavenging

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• catalysis in recent years not only with heavy metals such as ruthenium and iridium [1][2][3][4][5], but also with lighter elements [6][7][8]. This field of light-mediated organic transformations relies on the use of a photocatalyst to promote radical reactions through electron transfer between this former

• 9,10-dicyanoanthracene radical anion (DCA•−) [29]. This system effectively drives photoredox-mediated reduction and C–C cross-coupling reactions under mild red-light conditions with various aryl halides, an aliphatic iodide, and O- and N-tosylated substrates (Scheme 4a). The authors discuss two

• plausible mechanisms: a photoinduced electron transfer (PET) between the 3MLCT state of the copper complex and DCA or a triplet–triplet energy transfer (TTET) between the 3MLCT state of the copper complex and DCA. In both of these mechanisms, the involvement of a doublet excited-state of the radical anion

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• radical cations and dications of linear and angular [3]naphthylenes, consisting of fused aromatic naphthalenoid and antiaromatic cyclobutadienoid moieties and containing different degrees of paratropicity. Electronic absorption and vibrational Raman spectroscopies were used to describe the more relevant

• report that compounds 1 and 2 can both be easily oxidized to form relatively stable radical cations (1•+, 2•+) and dications (12+, 22+). Interestingly, oxidation reverses local antiaromaticity to aromaticity, a transition that is particularly noticeable in 1 → 1•+ → 12+, where stabilization of the

• dication is associated to the appearance of a global diatropic ring current which stabilizes the whole molecule. On the contrary, 22+ can be better viewed as two segregated radical cations with slight, but high enough, local diatropic character in each. Here, we use electronic UV–vis–NIR absorption and

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• (sp2)–H radical sulfenylation of enaminones or chromones has emerged as a popular strategy using various sulfenyl precursors such as thiophenols [38][39][40], sulfonyl hydrazides [41][42], disulfides [43], KSCN [44], S8 [45], methylsulfinyl derivatives [46], sodium sulfinates [47], and thiosulfonates

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

• ) exhibited a lesser effect. Considering that TEMPO, as an oxidizing agent, affected the reaction, it could be concluded that the reaction did not proceed through a free radical mechanism. Based on the results of the control experiments and the related literature [26][30][41][52], a possible mechanism for the

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• , Palestine 10.3762/bjoc.21.15 Abstract An efficient and eco-friendly approach for synthesizing difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles was established via a visible-light-promoted radical cyclization reaction. This method employed the readily accessible and inexpensive

• target products in good to excellent yields. Mechanistic studies revealed that the reaction proceeds via a radical pathway. Keywords: cyclization; difluoromethylation; hypervalent iodine; polycyclic imidazole; visible light; Introduction Organofluorine compounds continue to play important roles in

• both difluoromethylated and aryldifluoromethylated benzimidazoles. Inspired by previous work in radical chemistry, we turned our attention to difluoroacetic acid (CF2HCOOH) and α,α-difluorobenzeneacetic acid (PhCF2COOH), both of which are inexpensive and readily available industrial raw materials. In

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• nitrenoid intermediate was characterized by the same group [75]. Further radical rebound from INT-4 induces the enantioselective C–N bond formation. Finally, the desired product 2 is released from INT-4, regenerating the active chiral copper species to participate in the catalytic cycle. 1.2 C(sp2)–H

• Synthesis of primary amides via the generation of copper–imidate radical intermediates In a subsequent study, the research group of Son developed a method for the reduction of dioxazolones to synthesize primary amides under mild reducing conditions in copper catalysis (Scheme 10) [103]. The reaction was

• was proposed for the copper-catalyzed synthesis of primary amides. Dioxazolone first binds to the copper catalyst, forming the dioxazolone-copper complex (INT-34). The silane reductant then reduces INT-34, forming the copper imidate radical species INT-35, furnishing the formation of primary amides 28

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• electrochemistry and copper catalysis for various organic transformations. Keywords: copper; electrochemistry; radical chemistry; single-electron transfer; sustainable catalysis; Introduction Transition-metal-catalyzed cross-coupling has emerged as an effective method for forming carbon–carbon (C–C) and carbon

• remains a significant challenge owing to the high energy barrier required for oxidative addition and facile β-hydride elimination [12]. The development of radical approaches facilitated by transition-metal catalysis has provided a promising solution to overcome the limitations of conventional coupling

• reactions, particularly in controlling the high reactivity and selectivity of radical intermediates [13][14]. Early studies on copper-mediated radical reactions, such as Julia’s work on radical cyclization reaction [15], along with advancements in dimerization [16][17], oxidative cleavage [18][19], and

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• or radical (Figure 1). The latter is typically operative when the reaction is carried out under oxidative conditions, usually in the presence of O2 and TEMPO, involving the formation of radical species through single-electron transfer (SET) from a copper catalyst to a precursor. Subsequent addition

• reaction proceeds through an initial single-electron transfer from NFBS assisted by the active copper species, followed by intermolecular hydrogen-atom transfer from the carbazate. The nitrogen radical intermediate I thus formed is decomposed into the acyl or alkyl radical intermediates II and III

• , respectively. The latter interacts with the alkene generating an alkyl radical IV that converts to the cationic intermediate V by single-electron oxidation by the Cu(II) species. Finally, the attack of the nucleophile leads to the desired products 6. Starting from aryl carbazates, intermediate II, adds

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used

• a high decrease in the isolated amount of 3a, compared to the same experiment carried out in the presence of light, from 20% to 2% yield). Considering the potential occurrence of a radical pathway, additional experiments were conducted in the presence of galvinoxyl and TEMPO, powerful radical

• scavengers capable of abstracting the radical species that could emerge in the reaction media. The use of galvinoxyl proved to be insufficient to conclude since a control experiment showed that HIRs 2 decompose in the presence of galvinoxyl. When using TEMPO (Scheme 5), sulfinamide 6aa was not detected, but

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

• derivatives. Upon abstraction of a hydride from tris(trimethylsilyl)silane (TTMS) by an excited benzophenone derivative, the formed silane radical can undergo a XAT with an alkyl bromide to generate an alkyl radical. Consequently, the alkyl radical undergoes a Giese-type reaction with the Dha derivative

• ; Introduction The construction of C(sp3)–C(sp3) bonds is a highly important target in synthetic organic chemistry. Historically, polar conjugate additions have been a benchmark method for constructing these bonds by functionalizing an electron-deficient olefin [1][2][3]. Recently, however, radical-based

• approaches have also gained widespread attention for their unique advantages in these transformations [4]. Radical chemistry often exhibits complementary reactivity to two-electron pathways and can be performed with high selectivity, atom economy, and functional group tolerance [5]. A well-known radical

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

• derivatives, were synthesized using two reaction sequences (Table 1). The first sequence involved the chloroformylation of isoxazolones 3 to 5-chloroisoxazole-4-carbaldehydes 4 by POCl3/DMF [20][21][22][23], followed by radical chlorination of 4 with SO2Cl2/AIBN [24]. The alternative route to acid chlorides 1

• included oxidation of aldehydes 4 with Oxone to acids 5 and the conversion of the latter into acid chlorides with thionyl chloride. The first reaction sequence was suitable for obtaining compounds 1a–c,e,f with substituents tolerant to radical reaction conditions. A significant advantage of the method is

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

• antioxidant properties were determined by oxygen radical absorbance capacity assay (ORAC-FL), expressed as Trolox equivalents (TE) and using fluorescein as probe. Additionally, the study investigated the ability of the compounds to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in

• regulates kinases involved in the hyperphosphorylation of tau, contributing to neurofibrillary tangles. Meanwhile, melatonin is known for its neuroprotective properties, countering oxidative stress by scavenging radical oxygenated species and exhibiting potent antioxidant capacity [44][45]. The calcium

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• pentabenzocorannulene would produce air-stable radical and ionic PAHs, and that coupling such fragments would lead to stable redox-active carbon sheets. Conclusion In conclusion, the “surprise” in the surprising pKa for BIC and FIC was in our expectation of the deprotonated forms as poorly delocalized fluorenyl anions

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

• Jon Atiba Buldt Wang-Yeuk Kong Yannick Kraemer Masiel M. Belsuzarri Ansh Hiten Patel James C. Fettinger Dean J. Tantillo Cody Ross Pitts Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, U.S.A. 10.3762/bjoc.20.259 Abstract Selectivity in radical chain

• truncated after incorporation of two bicyclopentane (BCP) units. Synthetic and computational studies suggest this phenomenon can be attributed to alternating radical polarity matching. In addition, single-crystal X-ray diffraction (SC-XRD) data reveal structurally interesting features of the CF3SF4

• -containing [2]staffane in the solid state. Keywords: pentafluorosulfanylation; [1.1.1]propellane; radical chain oligomerization; staffanes; strain-release; Introduction In various radical additions of X–Y across [1.1.1]propellane (1), functionalized oligomers known as [n]staffanes – with n > 1, where n

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

• required and poorer yields afforded. The rationale for the difference in mechanism was attributed to the oxycyclisation to yield oxazolidinone oximes 63 occurring through an ionic mechanism, whereas the aminocyclisation takes place through a radical manifold, a difference that is triggered by the

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

• or transform into a long-lived radical cation by substrate reduction, which are the fundamentals of photoredox catalysis (Figure 13a). Monomeric porphyrins and supramolecular porous frameworks composed of porphyrin building blocks, such as metal-organic frameworks (MOF) and covalent organic

• and a photosensitizer, facilitating photoinduced electron transfer (PET) to form the active cation radical B, and intersystem crossing (ISC) for energy transfer to generate the triplet carbene C. Radical B then reacted with biradical C, producing the new radical D, which accepted an electron from the

• porphyrin radical anion. Ultimately, protonation of intermediate E led to the final product. Formation of intermediates, such as enamine A and cation radical B, was confirmed using techniques like ESIMS, 1H NMR, and EPR, Stern–Volmer quenching experiments, respectively. All these mechanistic studies

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

• units are easily modified by acylation, the hydrophilicity of the rotaxane crosslinker (RC) could be tuned in this manner. This [3]rotaxane crosslinker RC was added 0.5 mol % on the standard free radical polymerization of vinyl monomers to afford rotaxane-crosslinked polymer (RCP) (Figure 15B). Similar

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

• the radical Kharasch-type functionalization of organic molecules with OOR fragment including free-component radical couplings. The discussion has been structured by the type of the substrate of radical peroxidation: C(sp3)–H substrates; aromatic systems; compounds with unsaturated C–C or C–Het bonds

• . Keywords: C–H functionalization; oxidation; peroxidation; radical reactions; TBHP; Introduction Organic peroxides are used in many different areas of human activities. The traditional and most developed field is the use of peroxides as initiators in the polymerization process for the production of a wide

• peroxides, oxaziridines, and their derived species are often applied as terminal oxidants [7][8]. The weakness of the O–O bond allows alkoxy radicals to form through homolysis or reduction [9]. The generated alkoxy radicals provide an accessible tool for selective radical cascades, where a variety of

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• 4 (65%), 5 (50%), and 6 (40%) by chromatography was straightforward. However, the subsequent oxidation of the alcohol with the usual oxidizing agents (Jones reagent, KMnO4, etc.) was not successful. A radical oxidation with TEMPO, potassium bromide (KBr), sodium hypochlorite (NaOCl), and sodium

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

• synthetic organic chemistry, becoming indispensable tools in total synthesis, late-stage functionalisation and radiolabelling [1][2][3][4][5][6][7][8][9]. Due to their great mechanistic flexibility, including reactivity as oxidants, electrophiles, radical precursors and transmetalating agents, they often