Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• visible light. How to design a bioinspired approach may be most attractive to synthetic chemists. Recently, Tang [16] and Jia [17] independently reviewed their remarkable bioinspired total syntheses as accounts. Tang documented their longtime carrier of learning from nature aiming to achieve better

• invented. Moreover, bioinspired total synthesis involving visible light and enzymes are new significant trends in this field, and these techniques have demonstrated great power in achieving unprecedented selectivity and reactivity. Since nature still prevails in rapid generating molecular complexity and

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• thermal fuels have undergone significant advancements over the past four decades, emerging as a promising technology for light-to-thermal energy conversion. While these materials exhibit considerable development potential, critical challenges remain that hinder their practical implementation. In this

• ) through structural or bond rearrangements, thereby enabling solar energy storage. This reversible process is termed "energy charging", while the subsequent transformation of high-energy photoisomers back to their ground state – triggered by external stimuli such as light, heat, or catalysts – releases

• light-harvesting carbazole units with photoresponsive azobenzene units in a unique macromolecular architecture (Figure 4c) [48]. The resulting cross-linked polycarbazole structure led to a high solar thermal storage capacity of 179.9 J/g and an extended half-life at 60 °C, increasing from 7 min for the

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

• ; stereoselectivity; Introduction Photochemical reactions utilize light as a sustainable energy source and are considered to be ‘green’ reactions [1][2]. Organic chromophores absorb light, accessing higher-lying excited state(s) that exhibit distinct reactivities, leading to bond breaking and formation, irreversibly

• are closer to the range of irradiation wavelengths of the experimentally used light source (333–364 nm). For 1, this peak is closer to experimental absorbance, λmax = 338 nm [80]. The remaining peaks, shown in blue and green for S2 and S3, respectively, absorb at higher energy than the experimental

• light source. Electronic transitions to these excited states are impossible in the experiment and thus will not be considered for this photochemical mechanistic study. DBH photodenitrogenation mechanism We then turned our attention to the photochemical reaction mechanisms leading to the formation of

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

• 22, 14195 Berlin, Germany School of Natural and Environmental Sciences, Newcastle University, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK 10.3762/bjoc.21.153 Abstract Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed

• reactions have been developed. Employing the simple amine, DIPEA, as the terminal reductant, products resulting from overall 2-electron or 4-electron-reduction processes could be obtained using either a photocatalytic approach under blue light irradiation or directly under UV-A light irradiation without an

• additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product. Keywords: carbenes

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

• , C11, and C12 contiguous stereogenic centers, provided important insights that influenced the design of our second-generation total synthesis. Compared with the Snider-type radical cyclization using stoichiometric amounts of metal oxidants, visible-light-induced photoredox-catalyzed radical cyclization

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• of each reaction was thus 200 μL, with final concentrations of 100 mM (for substrates), 500 mM (for co-substrates) and 1 mM (for catalysts). After 48 h, the outcome of the reactions was determined by analytical UPLC–MS with, additionally, evaporative light-scattering detection [22][23] to enable

• subsequently used. Panel B: yields, estimated by evaporative light scattering detection, of reactions involving combinations of substrates, co-substrates and catalysts (dash: <2% estimated yield). Highlighted combinations (green boxes) were selected for mass-directed purification. aMultiple intermolecular

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• (c) MC3. (d) Molecular arrangements of MC3. Hydrogen atoms are omitted for clarity. (a) Absorptions and (b) emissions of compounds 3a, 3b, MC1, MC2, and MC3 measured in dichloromethane at room temperature. The inset shows the photographs under UV light at 365 nm. The concentration is 10 μM

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• photochemical and electrochemical methods, have been explored. Over the past two decades a variety of light-promoted imino-pinacol coupling reactions have been developed, involving the use of catalytic transition-metal complexes [35][36], organic dyes [37][38][39], and polyaromatic compounds [40][41] as

• purified through flash column chromatography on silica gel to give the isolated pure product. X-ray determined structure of chiral piperazine 2b. Synthesis of vicinal diamines via imino-pinacol coupling in the presence of metal-based reductants. Light-promoted imino-pinacol coupling for the synthesis of

• on a 0.1 mmol scale. Proposed reaction mechanism. Cyclic voltammetry investigation. Cyclic voltammetry of a 0.325 M solution of Et4NBF4 in DMF (light-blue line). Cyclic voltammetry of diimine 1a (10 mM) recorded in a 0.325 M solution of Et4NBF4 in DMF (dark-blue line). Cyclic voltammetry of diimine

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• ). Shining light will bring the molecule to a generic excited state (which is different for different photoswitch classes and substitution patterns and will not be treated in detail), which can then relax back to the ground state in either of the two wells. In cases where the two absorption spectra of the

• absence of light. Apart from some special cases where more competing mechanisms are operating [5], the thermal isomerisation typically is a first-order decay: Where I is the monitored signal at the time t, I0 the initial signal, and k the kinetic constant. Once k is known, the thermal half-life t1/2 can

• picoseconds to several years. The presence of heteroatoms also introduces H-bond donors and acceptors and metal coordination sites [11]. Like azobenzenes, E–Z isomerisation of azoheteroarenes can be triggered by light irradiation, while Z–E isomerisation proceeds through irradiation with a different

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• , antibacterial, and anti-inflammatory activities [10][11][12][13]. In the field of optoelectronics, especially with 2,4-diarylquinoline derivatives, extensive studies have highlighted their applicability in organic light-emitting diode (OLED) systems as functional materials [14][15] and cutting-edge fluorescent

• light of climate change and the ongoing energy crisis, there is an urgent need to reform energy and chemical production by prioritizing environmentally sustainable methods that are both practical and broadly implementable. Styrenes are industrially important bulk chemicals [39], with an estimated global

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

• release systems based on host–guest selective recognition, self-assembly, and nano-valves by the use of of calixarenes and pillararenes from five perspectives: pH, light, enzyme, hypoxia, and multi-stimuli combination responses. Furthermore, the article projects the future clinical application prospects

• in pH, light, and enzyme activity, the binding affinity between the guest and host molecules can be altered, thereby achieving controlled drug release and targeted delivery. (2) Drugs are loaded into self-assembled host–guest systems [29][30][31][32]. The chemical structure or properties of the host

• or guest molecules are altered upon exposure to specific stimuli, such as light, pH changes, or enzymes. This modification induces the disassembly of the host–guest complex, thereby releasing the encapsulated drugs. Fundamentally, this mechanism relies on controlling the assembly and disassembly

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• , ON, Canada). Reactions were monitored using thin-layer chromatography on aluminium-backed silica plates (Sigma-Aldrich) using either UV-light (254 nm), iodine, KMnO4, phosphomolybdic acid, or p-anisaldehyde for visualization. Tetrahydrofuran (THF) was dried and distilled over sodium/benzophenone

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

• ; photochemistry; Soon after its first reported synthesis in 1936 [1], [Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine) and its derivatives attracted significant attention due to their photophysical properties [2][3][4]. These complexes can efficiently absorb visible light through a metal-to-ligand charge transfer (MLCT

• in the presence of electron donors and acceptors. Furthermore, [Ru(bpy)3]Cl2 can engage in Förster and Dexter energy transfer processes, enabling the transfer of excited-state energy to molecules that do not themselves absorb visible light. This versatility is arguably the reason for the tremendous

• impact of [Ru(bpy)3]Cl2 on several research areas, including solar energy conversion [5], optosensing [6], photodynamic therapy [7][8] and bioimaging [9]. Scattered examples of [Ru(bpy)3]Cl2 being used as a photocatalyst for visible-light-driven organic synthesis appeared in the scientific literature as

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• perchlorate, as indicated in Figure 2 (X = O, Y, Z = Me). The possible coordination patterns are shown. NICS(iso) and NICSzz values at the molecular plane (z = 0) and 1 Å (z = 1) above this plane in a perpendicular direction. Points a–c correspond to the respective ring points, in light red. Perpendicular

• points at z = 1 are shown in light green. Calculateda absorption (λabs, in nm) and emission (λem, in nm) wavelengths of compound 19 at the free and barium perchlorate bound states, using different DFT functionals. Supporting Information Supporting Information File 51: Energies, calculated absorption and

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• %) as a light yellow solid. Rf = 0.73 (CHCl3/hexane = 1:2 v/v); 1H NMR (CDCl3, 500 MHz) δ 1.20 (s, 42H), 2.97–3.08 (m, 4H), 3.49–3.53 (m, 4H), 7.06 (s, 2H), 7.21 (s, 2H), 7.37–7.40 (m, 4H), 7.60–7.62 (m, 2H), 7.70–7.73 (m, 2H) ppm; 13C NMR (CDCl3, 125 MHz) δ 11.48, 18.84, 32.32, 32.57, 92.38, 93.65

• by recyclable HPLC (CH2Cl2 as an eluent) to afford (Sp)-4 (11.8 mg, 0.025 mmol, 45%) as a light yellow solid. Rf = 0.43 (CHCl3/hexane = 1:2 v/v). 1H NMR (CDCl3, 500 MHz) δ 2.98–3.09 (m, 4H), 3.39 (s, 2H), 3.43–3.55 (m, 4H), 7.09 (s, 2H), 7.21 (s, 2H), 7.37–7.41 (m, 4H), 7.62–7.65 (m, 2H), 7.70–7.73

• , respectively. Dimer (Sp)-6 (6.8 mg, 0.0062 mmol, 16%) was isolated from the first fraction by recyclable HPLC (CH2Cl2 as an eluent) as a light yellow solid. Trimer (Sp)-7 was isolated from the second fraction by recyclable HPLC (CH2Cl2 as an eluent). Further purification of (Sp)-7 was carried out using chiral

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

• processes underlying a wide range of applications, including artificial photosynthesis, solar energy conversion, and photocatalysis [1][2][3]. In particular, the formation of long-lived charge-separated states is crucial for efficient energy conversion and advanced photofunctions driven by light. Among

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

• ]. Thus, the use of visible light as an energy source provides more efficient chemical transformations and minimize the use of harmful reagents, the generation of waste and the consumption of energy, fulfilling several principles of Green Chemistry and promoting greener opportunities for organic synthesis

• [37][38]. In this context, the reactivity of enaminones under visible-light-mediated reaction conditions has attracted significant attention [39]. However, it is rather surprising that a photocatalytic approach for the synthesis of enaminones has yet to be explored. Herein, we report the first light

• while 3-iodochromone failed to provide the desired enaminone 9a (Table S7, Supporting Information File 1). Control experiments including the reaction in the absence of visible-light or photocatalyst, showed no product formation (Table 1, entries 16 and 17). Interestingly, the yield of 9a dropped to 30

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• . Keywords: azobenzene; protonation; sensing; spectral changes; temperature; Introduction Molecular switches are molecules that can reversibly shift between distinct (meta)stable states in response to external stimuli such as light, pH changes, or electric fields [1]. Over the past decades, they have

• emerged as staple building blocks in smart materials, from light-responsive norbornadienes in molecular solar thermal energy storage [2] to pH-sensitive spiropyrans in cell imaging [3], and redox-active viologens in memory junctions [4]. Among the different molecular switches azobenzenes stand out due to

• heavy metal detection [16][19] and humidity sensing [20]. The color changes can be either reversible or irreversible, depending on the mechanism of operation. Spectral tuning also enables switching with low-energy light, eliminating the need for potentially harmful UV irradiation [21]. Utilizing

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• switchable probe for light-driven reversible printing and erasing applications [29]. Besides exhibiting excellent photoswitching in solution phase, the tripodal photoswitches exhibit extended half-life of the ZZZ isomer in the solid-state as well [22][29]. The overall efficiency of the molecular switch could

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

• synthesis of benzamides via the arylation of isonitriles with diaryliodonium salts under blue light irradiation (Scheme 1C). Results and Discussion We commenced our investigation by the optimization of the reaction conditions. During the preliminary experiments we tested different solvents and solvent-to

• ones [31][32][33] introducing the photocatalyst [Ru(bpy)3](PF6)2, which successfully initiated the reaction under blue light irradiation and afforded benzamide 2aa in 36% yield (Table 1, entry 2). In that case less than 2% of the iodonium salt 1a remained in the reaction medium according to the 1H NMR

• [Ru(bpy)3](PF6)2 as the photocatalyst, under an Ar atmosphere with irradiation by blue LED light (Table 1, entry 2). With the optimized conditions in hands, a series of benzamides 2aa–je were synthesized using various symmetrical diaryliodonium salts 1a–k and isonitriles (Scheme 2). The analysis of

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• in applications such as organic light-emitting diodes (OLEDs) [8], circularly polarized luminescence (CPL) [9], and chiral photocatalysis [10]. In the past decade, heteroatom-containing helicenes have attracted increasing attention due to their tunable optoelectronic properties and potential

• polarized organic light-emitting diodes (CP-OLEDs) based on 40 demonstrated a |gEL| of 2.2 × 10−3, a narrow emission bandwidth (FWHM = 49 nm), and a maximum external quantum efficiency (EQE) of 31.5%, placing it among the highest-performing multiple-resonance-induced thermally activated delayed fluorescence

• -containing derivatives showed red-shifted emission, broader FWHM, lower PLQYs, and diminished BCPL values, indicating a trade-off between extended conjugation and emissive efficiency. Yin’s group introduced 1,4-BN motifs into compounds 51a and 51b, which emitted blue-green light at 474 and 465 nm

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• influenced by the structural variations and the environment (temperature, solvent properties, acidity and presence of other molecules). The E/Z isomerization of the azodyes, caused by light irradiation [12][13][14] or electrochemically [15][16], has paved the way for the development of innovative materials

• ][44][45] and systems for energy storage [46][47]. The phototautomerism of azodyes refers to the reversible isomerization process that occurs upon exposure to light, leading to exchange of a proton [48][49]. The obtained tautomeric forms have different optical and chemical properties, which make these

• part is flexible, the excitation of E can lead to E/Z isomerization, which competes with the initial excited-state PT process, reducing its efficiency [52]. The theoretical data, collected in Table 1, can shed light on the potential energy landscape in the ground state for the studied compounds

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• conducting polymers or scaffolds for drug synthesis. Among them, 1,3-dihydrobenzimidazoles are widely found in many materials, drug candidates, and catalysts. For instance, they can be used in organic light-emitting diodes (OLEDs) [38], as water-soluble antitrypanosomatid agents [39], or in the synthesis of

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

• polysubstituted oxetanes 64 (Scheme 18) [57]. The mechanism is based on a 1,5-HAT/radical recombination sequence where the H-atom transfer is triggered by an S0 → T1 excitation of the starting allyl ether 63 using an iridium photosensitiser and blue light for irradiation. The method employs mild reaction

• ] Cycloadditions Another widely used method for oxetane synthesis is the [2 + 2] cycloaddition between carbonyls and olefins (Scheme 19), and the two main variations include light-induced Paternò–Büchi reactions and Lewis acid- or base-catalysed formal [2 + 2] cycloadditions. The main advantages of these reactions

• performing the reaction under visible light irradiation, or coupling the reaction to other light-induced processes to produce new classes of products. In 2018, Aitken and co-workers reported a synthesis of previously unknown tricyclic 4:4:4 oxetanes 73 through a photochemical triple cascade reaction starting

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

• modified. In recent years, photocatalysis has been widely adopted due to its green and efficient nature [45][46][47][48][49][50][51]. The generation of amidyl radical is implemented by HRP. Six different methods (Figure 2c), which have been developed for visible-light mediated reactions, could generate

• (SET) process by the cleavage of the N–O bond; (c) direct homolytic cleavage of weak N–S or N–X bonds in HRP initiated in the presence of visible light; (d) the intersystem crossing (ISC) of S1 to T1 state directly from the amide anion. This review is organized by bond cleavage type, offering a deep

• demonstrated the homolytic cleavage of the N–O bond using N-(tert-butyl)-O-(1-phenylvinyl)-phenylhydroxyamide as a HAT reagent [78][79]. This compound was capable of initiating the formation of amidyl radicals through visible light activation. Although their controlled experiments showed that this method was