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

• proved to be suitable for the cyclization towards 35 and the eventual macrocyclization was achieved via coupling of the alkyl bromide unit with the thioester. Mechanistically, this reaction is enabled by the formation of an intermediate alkylzinc halide, which is produced by single electron transfer

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

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

• 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

• aniline furnishing acetylanilide 158 in 87% yield. A wide range of arylamines bearing electron-donating or electron-withdrawing substituents, as well as heteroarylamines, were also competent nucleophiles, delivering the corresponding amides 159–161 in good yields. EPR studies suggested a single-electron

• -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

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

• diradical at the unsaturated ketone (62a), cyclisation to form an intermediary highly substituted cyclopropane (62b) followed by single-electron transfer to the zwitterionic 62c and rearrangement to either the dense connectivity of lumisantonin (63), or carbocation capture by solvolysis of intermediate 64a

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

• in quinoline to generate hexahydroquinoline using a Ru catalyst (Scheme 8) [67]. When (S,S,S)-DKP was used as a ligand, the hydrogenation of the carbon ring was highly selective. Reduction of aromatic rings via hydride or electron transfer pathways Beyond catalytic hydrogenation, aromatic rings can

• also be reduced through hydride-based or electron-transfer pathways, which provide complementary modes of reactivity that are often orthogonal to metal-catalyzed hydrogenation systems. Classical dissolving-metal reductions such as the Birch reduction convert arenes into 1,4-dihydro intermediates via

• sequential electron transfer and protonation, enabling regioselective partial dearomatization that is difficult to achieve under hydrogenation conditions. Likewise, hydride reagents – including NaBH3CN, DIBAL-H, and other aluminum or borohydride derivatives – have been widely employed for the selective

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

• hydrogen atom from 1,4-cyclohexadiene to furnish the alcohol product. The active species Cp2ZrIII(OTf) is then regenerated via single-electron transfer (SET) from the Ir photocatalyst. Notably, the addition of thiourea 26 significantly improved the regioselectivity in this reaction. According to NMR

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

• and the acylazolium complex B (Ep = −0.81 V vs SCE), single-electron transfer (SET) reduction of B was thermodynamically feasible; however, the efficiency was found to be significantly low. The oxidation potential was measured to be around [Ep = +0.72 V] vs SCE, indicating that it is sufficiently

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

• involves a formal 1,3-C shift. Keywords: Aspidosperma alkaloids; [2 + 2]-cycloaddition/retro-Mannich reaction; DFT study; photoinduced electron transfer; Introduction Photochemical reactions, which enable the construction of topologically complex architectures from simple building blocks, have attracted

• valuable strategy for synthesizing natural and unnatural products from simple building blocks [4]. Three distinct photoinitiated approaches have been established for the formation of the [2 + 2] cycloadducts: direct irradiation [5][6], energy transfer (EnT) [7], and photoinduced electron transfer (PET, or

• intricacies of the key PET reaction for formation of the unique bicyclo[2.2.0]hexane unit present in the proposed intermediate L (Figure 1). In the presence of the excited photocatalyst [FCNIr(III)Pic]*, the substrate participates in an oxidative single-electron transfer (SET) process, which leads to the

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• bond cleavage to generate an N-imidoyl radical intermediate that undergoes intramolecular cyclization to yield the spirocyclic product (Scheme 1, path g) [14]. Notably, iron is known to exhibit similar behavior in single-electron transfer (SET) processes [15][16][17]. In fact, we previously

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• peaks appeared, indicating that photoelectron transfer occurred between iodine ions and the macrocycles [27][28], and fluorescence quenching was due to the photoinduced electron transfer (PET) effect between iodine ions and acceptors, resulting in non-radiative dissipation of excited state energy rather

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• , electron transfer from the pyrene to the dithienylethene acceptor occurs, quenching its fluorescence. Moreover, faster quenching was observed when the macrocycles were closer to the dithienylethene unit [59]. Considering the discoveries on tunable fluorescence, Alene and co-workers combined the

• dithienylethene is in the closed form, caused by photoinduced electron transfer (PET) from the fluorescent pyrene stopper to the acceptor dithienylethene (Figure 15). Moreover, the efficiency of the PET is modulated by the macrocycle shuttling motion between the two recognition sites due to differences in

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• can further undergo ring-opening or rearrangement reaction to assemble complex molecular frameworks. Additionally, quinone photoredox reactions involving single-electron transfer (SET) processes provide novel strategies for the stereoselective synthesis of useful structures such as spiroketals. This

• electron transfer for zwitterionic intermediate (e.g., (−)-106b or (+)-106b) formation; (2) protic solvents (e.g., MeOH) improve ee values through H-bonding stabilization, which reduces intermediate flexibility; (3) low temperatures enhance the optical purity by slowing conformational changes without

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

• include the use of transition metals or photoredox catalysts. In photoredox catalysis, radical generation often involves single-electron transfer (SET) to or from a photoexcited state of a photoredox catalyst, usually a metal complex or organic molecule. Two other notable strategies for radical generation

• catalysts. The drawbacks of chiral Lewis acids have been overcome to an extent using organocatalysis. The use of photochemistry to generate radicals by light-induced electron transfer has resulted in elegant enantioselective radical transformations. Several transition-metal photocatalysts [9] and organo

• ]. MacMillan obtained chiral free radicals by stoichiometric single electron transfer (SET) oxidation of enamines, formed by the reaction between chiral secondary amines and aldehydes. This mode of activation was called SOMO (singly occupied molecular orbital) catalysis and was employed in several organic

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

• ] generated [Cp2Fe]+ along with cathodic reduction of MeOH to H2 and MeO− acting as a base. Deprotonation of 1a using MeO− produced the anion A, which underwent single-electron transfer (SET) with [Cp2Fe]+ to give the nitrogen-centered radical B with regeneration of [Cp2Fe] [164][165][166][167][168][169][170

• -alkynylbenzamide 25 occurred to form the corresponding isoindolinone 26 in reasonable yields. According to the experimental results and previous investigations [209][210][211], the proposed reaction mechanism was described. Initially, proton-coupled electron transfer took place between n-Bu4NOAc and 2

• -diisopropylethylamine (DIPEA) to give the corresponding isoindolinone 28 in 32–90% yield. A plausible reaction mechanism was presented according to the experimental results and earlier works [213][214]. Firstly, the proton coupled electron transfer (PCET) procedure of 27 formed the amidyl radical B, which performed 5

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• starting materials for different types of reactions including thermal isomerization to cyclopentenes [36][37][38] and 1,4-pentadienes [37][38], chemical electron-transfer oxidations to cyclopentene [39] and cycloaddition reactions with electron-deficient alkenes and alkynes [38][40][41] (Scheme 1b

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• photocatalyst radical anion ([PC]·−) and the DIPEA radical cation D (Scheme 1). Single-electron transfer from [PC]·− to the benzoylazolium species 1 would then regenerate the ground-state photocatalyst and afford the Breslow radical anion C, which could in turn react with D in a hydrogen-atom-transfer (HAT

• conditions monitored over 48 h by 1H NMR. Plausible mechanism for the photocatalytic reduction of benzoylimidazolium salt 1 with DIPEA. [PC] = photocatalyst; SET = single-electron transfer; HAT = hydrogen atom transfer. Plausible mechanism for the photocatalyst-free reduction of benzoylimidazolium salt 1

• direct excitation of the benzoylazolium salt with the excited state species 1*, which subsequently reacts with TESH. Comparison of the redox potential of the silane (+1.54 V vs ferrocene) with the estimated excited-state potential of the azolium salt 1* (+1.70 V vs ferrocene) suggest that direct electron

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• times. This bis-vesicle structure possesses the following intelligent responsive characteristics: (1) temperature sensitivity originating from the enthalpy-driven nature of the host–guest interaction; (2) redox responsiveness due to the reversible electron transfer of MVC12; (3) competitive complexation

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

• Review article discussing photocatalysts capable of harnessing low-energy red light to trigger chemical reactions [19]. In addition to photoredox catalysis, several mechanistic platforms that leverage light – such as the use of electron donor–acceptor complexes [20], proton-coupled electron transfer [21

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• demonstrate that precise electronic and geometric design can enable controllable excited-state behavior in orthogonal molecular systems. Keywords: charge transfer; electron transfer; molecular dyad; transient absorption; Introduction Photoinduced electron transfer and charge separation are fundamental

• dynamics of these molecules, transient absorption spectroscopy measurements spanning the femtosecond to microsecond timescales were conducted. When electron transfer occurs between the donor and acceptor, the spin–spin interaction becomes weaker, facilitating the formation of triplet excited states upon

• the PTZ(TPA)2 moiety and the Pe radical anion almost instantaneously. The electron transfer occurs extremely rapidly (within the instrumental response function, <100 fs), likely via a direct CT transition. Subsequently, both signals showed growth components with time constants of 2.4 and 639 ps

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• . Simultaneously, acridinium photocatalyst PC1 absorbed energy and transitioned from the ground state to excited state under visible-light irradiation. This excited state PC1* is quenched by the amine, generating the amine radical cation and PC1 radical via a single-electron transfer (SET) process. Then, the C−Br

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• reactivity pattern in the current transformation, a reaction mechanism was proposed taking into the account the known data and control experiments (Scheme 4). Upon irradiation with blue light, the Ru(II) catalyst undergoes photoexcitation, followed by an oxidative single-electron transfer (SET) process with

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

• reduction of the Ni(II) pre-catalyst) via oxidative addition, radical coupling and reductive elimination. The last step is a single-electron transfer between the resulting Ir(II) and Ni(I) complexes, regenerating the active catalysts and closing the two cycles. In 2021, Romanov-Michailidis and Knowles et al

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• proton-coupled electron transfer process [59][60][61][62][63][64][65][66][67][68][69]. Following this process, the corresponding amidyl radical abstracts a hydrogen atom from the substrate, resulting in the conversion of the amidyl radical back to N-alkylbenzamide. This pathway creates a complete cycle

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

• -mediated process. Based on the experimental results, a detailed reaction mechanism was proposed (Scheme 8). The reaction begins with the oxidative cleavage of an α-C(sp3)–H bond in acetonitrile (15) by the Sc(OTf)3/Ag2O system, generating an alkyl radical A through a single-electron-transfer (SET) process

• the cathode. This deprotonation leads to the formation of a carbanion, which undergoes single-electron transfer (SET) with Cp2Fe+, resulting in the generation of a carbon-centered radical. This radical subsequently undergoes intramolecular cyclization with the aryl ring to form the final oxindole or

• plausible mechanism for the electrochemical radical cyclization is proposed in Scheme 18. Initially, a diethyl malonate radical A is generated through a proton-coupled electron-transfer (PCET) process at the anode, with the aid of K2CO3. This radical then adds to the C=C bond, forming alkyl radical

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• nitrilium salt 92 followed by carboxylate attack (93) and Mumm rearrangement (Scheme 27) [63]. Furthermore, Maruoka and co-workers (2020) developed a one-pot transamidation reaction catalyzed by Cu via acid fluoride 48 (Scheme 28) [64]. In this work, single-electron transfer (SET) between Selectfluor and