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

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• Scheme 28D, involving initial generation of a nitrogen-centered radical 165, which undergoes intramolecular addition to the pendant allene to form a vinyl radical intermediate 166. Subsequent interception of 166 by an N–Cl bond furnishes alkenyl chloride 164. 1.4 Reaction of alkenyl metals with chlorine

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• electrochemical cell distinguishes electroorganic synthesis from traditional organic chemistry methods. Particular attention is paid to the generation of radical intermediates via the oxidation or reduction of radical precursors [40][41][42][43][44][45][46][47][48][49]. In this regard, the anodic oxidation of

• approaches focus mainly on intramolecular radical cyclizations [42][54][55][56][57][58][59][60][61][62][63], while intermolecular [1][64][65][66][67][68] N–N coupling remains a poorly studied area. In addition to the preparation of azo compounds [69][70], intermolecular N–N coupling reactions are of

• direct anodic oxidation of dinitramide anion with the formation of N-centered radical A. Monitoring of the reaction potential during electrolysis under standard conditions using a reference electrode revealed that the measured potential ranged from 2.2 V (at the start of the reaction) to 2.4 V (at the

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• Vasudevan Dhayalan Department of Chemistry, National Institute of Technology Puducherry, Karaikal-609609, Puducherry, India 10.3762/bjoc.21.200 Abstract Over the past two decades, organocatalyzed visible-light-mediated radical chemistry has significantly influenced modern synthetic organic

• chemistry. In particular, dual catalysis combining N-heterocyclic carbenes (NHCs) with organophotocatalysts (e.g., 4CzIPN, eosin Y, rhodamine, 3DPAFIPN, Mes-Acr-Me+ClO4−) has emerged as a powerful photocatalytic strategy for efficiently constructing a wide variety of carbonyl compounds via radical cross

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• deprotection, afforded enal 42. To avoid the chemoselectivity issues in the subsequent allylic oxidation and radical cyclization steps, enal 42 was converted to 43 by reduction of the aldehyde and protection of the resultant diol with Ph2SiCl2. Allylic oxidation of 43 with 44 [37] afforded the enone in 22

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• -ryanodol, cinnzeylanol, and cinncassiols A,B In 2014, the Inoue group at the University of Tokyo reported a synthetic strategy for ryanodol (4) that leveraged substrate symmetry design, employing intramolecular radical coupling and olefin metathesis as key steps [46] (Scheme 4). Recognizing an embedded

• -alkoxy bridgehead radical addition then installed an allyl fragment, and ring-closing metathesis (RCM) smoothly formed the C ring to complete the core skeleton. The total synthesis was finalized by installing the four remaining stereocenters (C2, C3, C9, and C10). The specific synthetic route is as

• hemiacetalization to construct the oxa[3.2.1]-bridged ring system, thereby forming the D and E rings. Subsequently, the introduction of a tertiary hydroxy thiocarbonate at C11 afforded compound 38. Under thermal conditions, 38 underwent smooth introduction of an allyl fragment via intermolecular radical addition

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• (2) and C (3), featuring a visible light-catalyzed radical cation cascade for the formation of the C8–C8′ and C2–C7′ bonds [6]. Subsequently, they improved the reaction conditions to achieve the racemic synthesis of aglacins A (1) and E (4) as well [7]. In 2021, the Gao group described the total

• relies on a non-photocatalysis approach. Results and Discussion Retrosynthetic analysis of (+)-aglacin B Based on the retrosynthetic analysis shown in Scheme 1, both C8′–C8 and C7–C1 bonds in (+)-aglacin B (2) could be constructed in one-step from the β-bromo acetal 5 by a Ni-promoted tandem radical