Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• governed primarily by bond dissociation free energies, radical stabilization, and cage escape or recombination kinetics, rather than by inner-sphere insertion chemistry. In addition, in certain systems, hydride transfer can operate as a distinct mechanistic mode, wherein the M–H unit directly delivers a

• radical-type pathways. Mechanistically, these pathways depart from the classical two-electron noble-metal hydrogenation paradigm and instead operate through low-valent or electronically flexible intermediates, often involving single-electron or electronically asynchronous reactivity, enabled by the

• , and the successful late-stage electrohydrogenative functionalization of structurally complex molecules and drug derivatives further underscored the practical applicability of this strategy in medicinal chemistry contexts. To probe the involvement of catalytically relevant Fe–H species, radical probe

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• nitroxide-mediated polymerization (NMP), because shielding with ethyl or bulkier alkyl groups decreases accessibility of the nitroxide moiety and improves the equilibrium parameters in the reversible trapping of alkyl radical of the growing polymer chain [11]. This shielding also alters the redox properties

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• , including copper–amido-mediated nucleophilic addition or aminocupration, Lewis acid-type alkene activation, and radical-mediated pathways. These complementary mechanisms provide access to diverse alkene classes with control over regioselectivity (Markovnikov vs anti-Markovnikov addition), stereoselectivity

• metals such as palladium or rhodium, copper offers exceptional mechanistic versatility. The accessible Cu(I)/Cu(II)/Cu(III) redox manifold enables classical two-electron pathways and single-electron radical processes within broadly similar catalytic environments [28][29]. This flexibility is particularly

• electrophilicity and lowers the barrier for nucleophilic attack (Scheme 1b). Further, copper can mediate radical-based pathways either by generating hydrogen radicals or intercepting nitrogen-centered radical intermediates in oxidative- or photoredox-assisted systems (Scheme 1c). These radical manifolds often

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• auto-accelerating radical chain mechanism, to give a stable hydroperoxide complex 23 that was characterised by X-ray diffraction. This reaction was greatly accelerated by AIBN as radical initiator which generates Au(II) radical cations [(P^C^P)Au]+•, as well as RO• and ROO• radicals, which propagate

• complexes of type 8 can react with acetylenes slowly, in a possibly light-induced radical reaction [49]. The addition of radical initiators such as azobis(isobutyronitrile) (AIBN) reduced the reaction times from days to minutes, with quantitative and completely stereoselective formation of Z-vinyl gold

• calculations. Using the same radical-initiated approach it was also possible to realise gold hydride insertions of alkenes [65] and of isocyanides (Scheme 11) [66]. A different reactivity was observed for C^C-stabilised hydrides, with H trans to anionic C. The complexes (C^C)AuH(L) 19 (L = PMe3, Ptol3) and [(C

Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity

• Daria A. Burmistrova,
• Vasiliy A. Fokin,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Maxim V. Arsenyev,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65

• -withdrawing nature of the S=O group. The second redox stage characterizes the transformation of the sulfoxide fragment and is observed in most cases at 1.82–1.91 V. The radical-scavenging activity and antioxidant properties of the unsymmetrical sulfoxides and their precursor thioethers were evaluated using

• the reaction with the 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+•). In both assays, the lowest IC50 values among the studied catechol sulfoxides were found for compounds bearing isopropyl and tert-butyl substituents

• activities and unusual physicochemical properties, which render them useful in various fields of chemistry. Catechol-containing compounds, in particular, are known for their antioxidant activity through the regulation of free-radical processes [1][2], and are used as antiparkinsonian [3][4][5], antitumor

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• ) with NBS (N-bromosuccinimide, X equiv), FeBr3 (1.0 equiv), n-Bu4NBr (Y equiv), and TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl free radical, Z equiv) in solvent (2 mL) at the desired temperature was conducted for 23 h or 2 h. After the reaction, the typical work-up procedure was carried out and the

• , and solvent were examined (Table 1, entries 3–12). Because there was a possibility that a bromine radical was involved, TEMPO was used for the purpose of the ratio-control of E and Z isomers. TEMPO was found to have a tendency to suppress the generation of Z-2a in CH2Cl2 (Table 1, entries 6 and 8) [20

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• corresponding radical anion [27]. In contrast, possible reduction of an aliphatic ester substituent, such as our acrylate pendant, generally requires more negative potentials [28]. On the other hand, the first oxidation observed at ca. +1.47 V is most likely associated with the alkoxy donor fragment, in

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• used as a bleaching agent in the dyeing industry for more than a century [5][6]. Over the last 10 years particularly, it has begun to join the toolbox of reagents in organic synthesis, and shows diverse reactivity. It has been employed in reductions, radical processes and as a reagent for C1 transfer

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• chlorooxoacetate to give 14a/b in 84% yield, which were subjected to the radical deoxygenation conditions (AIBN, n-Bu3SnH) for 13-hydroxy removal, affording two deoxygenated products that were difficult to be separated from each other. Without further purification, the obtained mixture was treated with tetra-n

• bond of 15 was confirmed to be Z based on the NOESY correlations between 13-H/20-H3. The formation of product 15 could be attributed to the isomerization of the C13 allylic radical, generated by methyl oxalyl ester deoxygenation step, to the C11 allylic radical, followed by hydrogen abstraction from n

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• conditions using an inexpensive and atom-efficient CF3 source, trifluoroacetic anhydride, in ethyl acetate as a green solvent. An organic cyanoarene photocatalyst enables efficient CF3 radical generation under blue-light irradiation, providing a broad range of trifluoromethylated arenes and heteroarenes. The

• reaction displays pronounced sensitivity to substituent patterns rather than electronic effects. Mechanistic investigations, including radical trapping, Stern–Volmer analysis, and DFT calculations, support a reductive quenching pathway involving photocatalyst-mediated reduction of TFAA. The protocol is

• that CF3· behaves as an electrophilic radical [31][32], it was expected to react preferentially with electron-rich substrates compared to electron-neutral or electron-deficient ones. To probe this trend, trifluoromethylation was examined with substrates bearing donor substituents (methoxyarenes) and

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• primarily anthracene derivatives and benzyl C–H bonds, suggesting potential systematic errors in QM computations or experimental measurements. Radical and cation stabilities generally follow the trend: tertiary > secondary > primary methyl carbon stability. Our study also explores the correlation between

• ). Many of these transformations are not formal hydride transfers; however, they commonly involve buildup of positive charge (e.g., via metal–carbene/nitrene insertion transition states, radical cations, or polar hydrogen atom transfer). Hydricity could therefore serve here as an empirical reactivity

• reactive sites, where one of them is the correct site. Not surprisingly, the two reactions where the use of BDEs lead to the correct predictions are photocatalysed and generally thought to involve radical formation. In general, the sites of lowest hydricity and BDE only coincide in three cases (compounds 5

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• combination of hydrogen peroxide with ferricyanide reacts with the phenol in a dioxygenase like reaction [12] to give a dioxetane a, followed by opening of the aromatic ring to form the oxonol anion b in alkaline solution, thus explaining the purple color. Oxidation of b leads to the delocalized radical c

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• 166 via radical cyclization, then the TBDPS-protecting group was cleaved and the obtained alcohol oxidized to aldehyde 167. The Cr(II)/Co(II)-induced asymmetric NHK coupling mediated by 172 with vinyl iodide 171 led to tetrahydrofuran 168. Protection of the secondary alcohol enabled the conversion to

• )-methyl-2,3-dihydroxypropanoate, respectively (Scheme 18) [93]. Again, Nicholas etherification of both starting materials was conducted to afford 175 in 5:1 dr. The major isomer was further transformed to 176 in a microwave oven via Kornblum oxidation. Radical cyclization and DMP-oxidation yielded

• also considerable amounts of 183`s epimer were formed (2:1 dr). Oxidation with DDQ removed the Bn-moiety (184) and triggered ketalization towards 185. Eventual mesylation formed key fragment 186 in 95% yield. For the assembly of both heterocyclic subunits of 186, Nicholas etherification and radical

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• radical cyclization (prostaglandin D2 metabolite, Jun Huang et al.), reductive cyclization cascade (aglacin B, Jina Xiao, Yu Peng et al.), electrochemical cyclization (review, Bin Li, H. N. C. Wong, Xiao-Shui Peng et al.), photochemical reactions (review, Shao-Min Fu, Bo Liu et al.), carbene insertion

• (vibralactone, Zhi-Yun Liu, Hong-Dong Hao et al.), interrupted [2 + 2]/retro-Mannich (aspidosperma alkaloids, Zhen Yang, Zhong-Chao Zhang et al.), dipolar cycloaddition (malayamycin A, Sha-Hua Huang, Jian Jin, Ran Hong, et al.), Zr-mediated radical transformations (review, Hugh Nakamura and co-worker)]. The

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• bond (Figure 2b) [30]. At the same time, Yang et al. presented a domino radical reaction of CH2-active compounds II and N,N-dimethylanilines III promoted by di-tert-butyl peroxide (DTBP), allowing the formation of the ethylene link via a domino-process of the methylenation and subsequent aminomethyl

• radical addition (Figure 2c) [31]. In the continuation of our work on application of pyrrolidines as sacrificial framework for the alkylaminomethylation of enones [32][33] we turned our attention to active methylene compounds IV as precursors of pyrrolidines. Preliminary experiments demonstrated that the

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• products were detected under the optimized conditions (Scheme 2). Based on our previous reports [48][56], DFT calculations, and cyclic voltammetry (CV) analyses (Figure 1), anodic single-electron transfer (SET) is expected to occur first from 3, generating the electrophilic radical cation [3]·+ as 3 (Eox

• = 0.735 V vs Fc/Fc+ in CH2Cl2) is oxidized more readily than the 2-naphthol partners (Eox of 4a = 1.081 V and Eox of 4b = 1.286 V vs Fc/Fc+ in CH2Cl2). The radical cation [3]·+ then undergoes rapid deprotonation to form a neutral radical intermediate (Int-I) with high spin density at the reactive site

• , enabling regioselective intermolecular coupling with 4. While a Scholl-type coupling-first scenario cannot be ruled out, the computed acidity of [3]·+ (pKa ≈ −5.2) together with the more spin-density localization in Int-I supports a deprotonation-first, neutral-radical pathway, consistent with related

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• -transfer (SET)-driven mechanism. Coordination of the arylamine to the potassium cation followed by deprotonation generates potassium amide salt AB. A SET process forms amine radical AC, which then transfers an electron to the amide, generating radical anion AD. Coupling of AC and AD forms a tetrahedral

• a radical pathway. Selectfluor undergoes a single-electron transfer (SET) with Cu(II) to generate the dicationic radical species AI, which abstracts a hydrogen atom from the PMB group to form a benzylic radical intermediate AJ. A subsequent SET process generates an acyliminium intermediate AK, which

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• , Novosibirsk, 630090, Russia 10.3762/bjoc.22.22 Abstract Rotational correlation time is a key parameter for organic radical contrast agents (ORCA) for magnetic resonance imaging (MRI). Design of polycyclic systems with incorporated nitroxide moieties in which rotation of the radical separately from the

• by ascorbate showed that the formation of the rigid tricyclic framework does not lead to a significant increase in stability of the radical center to chemical reduction. Keywords: annulated tricyclic system; nitroxide; pyrazole; pyrrolidine; triazole; Introduction Stable nitroxides are functional

• components of many high-tech materials, such as energy storage and organoelectronics devices [1][2][3][4][5][6][7][8], catalysts [9][10], bioactive coatings and nanoparticles [11][12], organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI) [13][14], etc. For these applications, numerous

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• synthesis, are gathered. Our definition includes both radical and polar ring-size altering reactions, transannular cyclisations of macrocycles and cation-mediated rearrangements where fitting. Goal of this review is to gather and compare mechanistic proposals for the biogenesis of ring-size-altered

• the methyl groups residing at C-4 and the C-7 methylene to ent-7α-hydroxykaurenoic acid (34a). The hydroxy group in 34a can further engage with a CYP450 enzyme at C-6 (different CYP isoforms responsible in different genii) to form an alkyl radical 34b which upon further SET forms an intermediate

• by the enzyme BscF, triggering a Wagner–Meerwein rearrangement after radical-polar crossover (38a to 38b) and elimination at the bridgehead methyl, resulting in the exo-olefin. The final intermediate 38c is further elaborated by enzymatic oxidation to give brassicicene C (39) from brassicicene I (38

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• double-bond character of the benzocyclopropene framework [30][31]. The reaction likely operates through an initial dearomative radical diiodination followed by a norcaradiene–cycloheptatriene rearrangement. Leveraging this enhanced reactivity, benzocyclopropene engages in inverse-electron-demand Diels

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• ). Therefore, the reaction is most likely not proceeding via a free radical mechanism. To clarify the influence of the amide group on the developed transformations, dihydrothiophene 4g bearing a sulfonylimine group instead of an amide was treated with sodium methoxide in methanol or with sodium ethoxide in

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• to produce 4. This reaction sequence would mediate the oxidation of the tolyl methyl group of 3 to an aldehyde without the use of chromium(VI). Benzylic bromination of 3 was accomplished using a combination of a radical initiator and a bromine source. Initial optimization of the benzylic bromination

• , this work performs the oxidation of the methyl group in 4-bromo-2-nitrotoluene to an aldehyde using a strategy of radical bromination followed by a Kornblum oxidation to give 4-bromo-2-nitrobenzaldehyde. This transformation eliminates the need for a chromium trioxide-mediated oxidation and the expenses

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• rearrangement and Lewis acid-promoted acetal–ene reaction provided the tetracyclic skeleton 101. With 101 in hands, a 6 step transformation afforded the alkyne 102 in an overall yield of 45%. After obtaining 102, the authors used a free radical reaction to initiate a one-step 6-exo-trig cyclization

• chloride, and radical reduction. Subsequently, reduction of the cyanide group with DIBAL-H and a Wittig reaction afford alkene 114 in 82% yield. Sodium metal was then used as a single-electron reducing agent to provide the second cycloaddition precursor 115, which was converted to the enamine. The enamine

• ]. Starting from pyridine derivatives 129, they obtained the key intermediate 131 via a Simmon–Smith reaction and a bimetallic-mediated photocatalytic radical coupling reaction. Intermediate 132 was then constructed by Friedel–Crafts alkylation using diethylaluminum chloride as a Lewis acid. The pyridine ring

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• Hiroshige Ogawa Hugh Nakamura The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, New Territories, Hong Kong SAR, China 10.3762/bjoc.22.3 Abstract Radical reactions, which have been reported in large numbers in recent years, have exerted major influence across fields

• and discovery of two-electron ionic transformations dominated the early stages. Over time, pericyclic reactions exemplified by the Woodward–Hoffmann rules and one-electron radical processes became prominent research topics. Today, many of these classical transformations have been further refined to

• afford reactions that are cheaper, safer, and less toxic. In this context, we focus on mild radical reactions mediated by zirconium (Zr), which has recently attracted attention because of its low toxicity and ease of handling. We discuss the utility of Zr in such radical processes and consider prospects

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• isomer of anion 2 we analyzed the structure of its highest occupied molecular orbital (HOMO) and the distribution of the electrophilic Fukui function (f–) [28] – the difference in electron density between the anion and the derived radical by abstraction of one electron (Figure 2). Both approaches

• possibility of i-halogenation via a chain radical mechanism (Scheme 3). The initiation stage includes an oxidation of anion 2 into the corresponding radical 13 which in turn reacts with halogens to form products 4a,b and a halogen atom which can also oxidize the anion. Quantum chemical calculations revealed

• negative free energy changes for all the stages of this reaction. A chlorination experiment with 2,2,6,6-tetramethylpiperidinyloxyl revealed a trace amount of a trap product detected by high-resolution mass spectrometry to support the radical mechanism. However, this does not exclude the possibility of a