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

• -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

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• formation of IN1. The radical cation IN1 served as the reference point for DFT investigations. As illustrated in Figure 2a, facilitated by a favorable radical cation–π interaction [31], IN1 proceeds to the first radical addition transition state (TS1), with an energy barrier of 8.3 kcal/mol. This leads to

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• metalloradical-catalyzed radical cyclization reactions. Enantioselective radical chaperone catalysis. Enantioselective radical addition by decatungstate/iminium catalysis. An ene-reductase-catalyzed photoenzymatic enantioselective radical cyclization/enantioselective HAT process. Photoenzymatic oxidative C(sp3

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• radical initiated intramolecular cascade cyclization of 1,n-enynes to provide structurally diverse heterocycles (Scheme 4) [11]. Solvent selection dictated divergent reaction pathways under I2/TBHP oxidation. When an acetonitrile/water mixed solvent was used, iodine radical addition to the alkyne

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• -exo-dig N-radical addition into the C≡C bond to generate the cyclic species C. The radical anion D was then obtained via single electron reduction of C at the cathode. The subsequent protonation of D gave α-aminyl radical E [215][216][217], which was converted into the anion F by further cathodic

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• and aldehyde 37, which was prepared with 9 steps from commercially available (+)-citronellol, underwent a Reformatsky-type radical addition under the conditions of Et3B/air/Bu3SnH to deliver aldol product [16]. Dehydration of the secondary alcohol gave (E)-38. The HAT radical cyclization [17] of 38 in

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -deficient [28], thereby lowering the energy barrier for electrophilic radical addition. Increasing the reaction temperature to 70 °C proved detrimental, yielding only trace amounts of product 14 (Table 1, entry 5). Finally, replacing Mn(OAc)3·2H2O/Cu(OAc)2·H2O with other oxidants, such as ceric ammonium

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• synthesis of esters of phosphonous or alkylphosphinic acids [33][34][35]. Only a single application of cesium hypophosphite was shown in the literature. CsH2PO2 was prepared in situ and used for formation C–P bond by radical addition to unsaturated carboxylic acids [36 ]To summarize the above, it is crucial

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• , and flow chemistry are being harnessed to push the limits of light-driven reactions [36]. Terada and colleagues show in this thematic issue how flow chemistry is used to significantly improve the yield of a π-Lewis acidic metal-catalyzed cyclization–radical addition sequence [37]. Recently, chemists

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• /Williamson etherification sequence (Scheme 8) [43]. In this case, however, the radicals were generated by irradiation of α-acetyloxy iodides 36, formed by treating the corresponding ketone precursors with acetyl iodide in the presence of catalytic Zn(OTf)2. The radical addition employed electron-rich alkenes

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• for constructing quaternary carbon centers in oxindoles via an N-heterocyclic carbene (NHC)-catalyzed intermolecular Heck-type alkyl radical addition and annulation reaction (Scheme 47) [28]. The reaction proceeds through a redox-neutral mechanism, where the NHC catalyst serves a dual role as both a

• cation B and an α-carbon radical A. The α-carbon radical A then undergoes intermolecular radical addition to the acrylamide, forming a new carbon-centered radical intermediate C, which subsequently undergoes intramolecular cyclization to yield the oxindole product 88a via homolytic aromatic substitution

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• , with particular attention to the 1,2-difunctionalization of olefins by alkyl halides via atom transfer radical addition processes in the presence of amorphous nitrogen-doped carbon dots (Scheme 1a) [20]. In the framework of this research topic, we decided to investigate the use of carbon dots as

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• surprisingly, 5e showed only traces of 8, even with an E*ox of −1.85 V (Table 2, entry 5). Under the oxidative quenching study, we also evaluated the photocatalytic potential of the new family of D–A compounds in the atom transfer radical addition (ATRA) reaction involving styrene and tosyl chloride (TsCl), as

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• barrierless thiyl radical addition and intersystem crossing (ISC) to furnish the final product. In contrast, acetonitrile’s polar aprotic environment destabilizes the carbene pathway, favoring direct reduction of the diazo moiety via electron transfer from the thiol. This solvent-gated selectivity underscores

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• et al. [59] reported an electrochemical method for the synthesis of phosphorylation of oxindoles and indolo[2,1-a]isoquinoline-6(5H)-ones using Cp2Fe through a radical addition/cyclization reaction at room temperature under argon gas. This research shows that this method is effective with various

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

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

• transformations have been addressed by Gianetti et al. such as C(sp3)–H oxidation, intermolecular atom transfer radical addition and C(sp)–H arylation using red light and DMQA (Figure 14), hence showing the great versatility of this photocatalyst. Red-light photocatalysis in biological systems Photochemical

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

• (II)–N3 complex 60. The azidyl radical 62 then reacts with N-arylenamine 57 via radical addition. Thereafter, it undergoes oxidation to form a kinetically labile vinyl azide intermediate 64. This vinyl azide intermediate 64 dissociates, yielding Cu(II) iminyl complex 65 via denitrogenation

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

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

• slight increase in chemical yield. Giese reaction: Radical addition on olefins with an electron-withdrawing group (EWG) followed by a HAT or SET and protonation; halogen-atom transfer: (a) tin-mediated XAT, (b) XAT initiated by a photocatalyst (PC) and mediated by boranes (B), silanes (Si) or alkylamines

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

• challenges in the synthesis of [n]staffanes using excess [1.1.1]propellane (1). (Bottom) selective synthesis of [2]staffanes bearing the SF5 (2) and CF3SF4 (3) groups (this work). Computed free energy profile for the oligomerization of [1.1.1]propellane (1) following SF5 radical addition at PWPB95-D4/def2

• -QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory. Computed free energy profile for the oligomerization of [1.1.1]propellane (1) following CF3SF4 radical addition at the PWPB95-D4/def2-QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory. (A) The molecular structure of 3 at 90 K with 5 independent

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

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• literature, oxacepham scaffolds, the 6-membered fused bicyclic analog of clavams, were prepared from appropriately substituted unfused precursors by intramolecular C-radical addition to alkene functionalities [44]. The utilization of radical conditions has prevented the effective nucleophilic opening of the

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

• radical; isocyanide; radical addition; radical cyclization; Introduction Carbon monoxide is a very important C1 resource in both synthetic and industrial chemistry and is not only capable of reacting with a variety of active species such as carbon cations, carbon anions, and carbon radicals (Figure 1

• to imidoyl units generated in situ by radical addition to isocyanides, innovative molecules with a variety of functions can be obtained. In other words, if functional groups can be prepared simultaneously with the formation of an imidoyl group, it would be an extremely useful method for the synthesis

• the combination with groups 15–17 interelement compounds would be considered effective for the generation of groups 13 and 14 heteroatom radicals. Radical addition of group 17 compounds to isocyanides If isocyanides (RNC) can undergo a radical addition of hydrogen halides (HX) and molecular halogens