Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• ring was then constructed via an intramolecular reductive Heck reaction from vinyl bromide 10 with exclusive regioselectivity. Considering the strain of forming the 7-membered ring, this highly efficient 7-endo-trig (vs 6-exo-trig) transannular Heck cyclization reaction was remarkable to be realized in

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• activated alkyne in an endo-dig fashion, forming a 7-membered ring. The resulting intermediate B undergoes proton transfer from the second pyrazole nitrogen to the vinyl silver moiety yielding pyrazolo[1,5-a][1,4]diazepine 16a and regenerating the silver catalyst. Methylation of either pyrazole nitrogen

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

• N,N-disubstituted acrylamides [30]. Catalyst-tuned regio- and enantioselective C(sp3)–C(sp3) coupling [31]. Catalyst-controlled annulations of bicyclo[1.1.0]butanes with vinyl azides [32]. Solvent-driven reversible macrocycle-to-macrocycle interconversion [39]. Unexpected solvent-dependent

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

• anode and phosphonate anion at the cathode (Scheme 12). The C(sp2)–X in aryl and vinyl halides is suitable in organic coupling reactions that are usually active in electrochemical environments. The use of combined electrodes is one of the creative methods in electrosynthesis processes. Léonel et al. [57

• ] reported an electrochemical coupling reaction of aryl and vinyl bromides with different types of alkyl H-phenylphosphinates in the presence of NiBr2 as a catalyst. The reaction was carried out with an alloy of Ni-Fe as the anode and nickel as the cathode in an undivided cell at a constant current for 0.5–2

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• (8), MsOc3HBC (14), and MsOc3HBC-vinyl (22)) as reported previously [11]. Nine more HBC derivatives with altered handle lengths and different electrophilic groups are introduced in this study. Furthermore, we include an evaluation of the efficiency of all reactive fluorophores (previously introduced

• provide fluorophore 19. Subsequent palladium-catalyzed cross-coupling with tributyl(vinyl)tin resulted in the installation of the vinyl group (compound 20). Finally, cleavage of the silyl ether gave the free alcohol 21, which was converted into the corresponding mesyloxypropyl HBC ligand 22. The

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• styrenes with diverse electronic properties as well as those containing sensitive functional groups such as esters, amides, and vinyl halides, to yield the desired β-chiral olefins in high enantioselectivity. Notably, the methodology could even be applied to vinylferrocene and vinylsilane derivatives

• calculations. The first hydroboration catalytic cycle is initiated by L*CuH species (L* = a chiral ligand) formed in situ through the combination of CuBr, LiOMe, and HBpin in the presence of a chiral ligand. Subsequent alkyne migratory insertion provides a vinyl cuprate intermediate Int B, followed by σ-bond

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• switching efficiency in aqueous solutions. In order to investigate the chemistry of this promising photoswitch and to unlock further applications, we now investigate strategies for the synthesis of derivatives, which are based on cross-coupling reactions. Fourteen vinyl-, aryl-, cyano-, and amino

• provides good yields of 65% and 71%, respectively, for the vinyl N-acetyl diazocine 8 (Table 3). An alternative way of vinylating N-acetyl diazocines is the Pd-catalyzed vinylation with polyvinylsiloxanes and TBAF as activating agent following the method by Denmark et al. giving rise to even higher yields

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• which the thiosulfonate was cleaved and then dimerized to form the disulfide. The reaction of sodium p-toluenesulfinate and styrene resulted in the generation of the corresponding vinyl sulfone (Scheme 5, reaction 2), suggesting the formation of p-toluenesulfonyl iodide during the reaction [50][51

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• copper catalyst, providing the vinyl copper intermediate INT-30. This intermediate then undergoes oxidative addition to the N–O bond of the dioxazolone to generate INT-31. Subsequently, decarboxylative reductive elimination occurs, forming the copper imidate INT-32. The active copper species is

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

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• and sulfur dioxide afforded vinyl sulfones with excellent regio- and stereoselectivity (Scheme 9) [22]. The authors used DABCO(SO2)2 to generate sulfur dioxide, and visible light irradiation and the mandatory presence of a photocatalyst for this transformation suggested a radical mechanism. The

• corresponding saturated compounds. Subsequent nucleophilic addition of the cyclic vinyl ether to the iminium salt generates an intermediate XXI susceptible of intramolecular electrophilic attack to give a tricyclic structure XXII. The final deprotonation provides the desired product 24. The multicomponent

• of α-substituted propargylamines 10. Synthesis of N-propargylcarbamates 11. Synthesis of (E)-vinyl sulfones 12. Synthesis of o-halo-substituted aryl chalcogenides 13. Synthesis of α-aminophosphonates 14. Synthesis of unsaturated furanones and pyranones 15–17. Synthesis of substituted

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• , utilizing a custom Python package developed in-house [53]. This approach enabled us to track the conversion process at different residence times. Specifically, we quantified the conversion by analyzing the area under the curve (AUC) of the Raman-active vibrational modes associated with the styrene–vinyl C=C

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• different electronic properties (18, 25–41, Figure 6) were screened as catalysts for the sulfa-Michael addition of tert-butyl benzylmercaptan 42 to phenyl vinyl sulfone (43). Without the addition of a porphyrin, no product was formed. Among the non-alkylated porphyrins (18, 25–32) only the ones containing

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• a major content of the material, Takata and co-workers developed the rotaxane crosslinker, which can be integrated as a small content on vinyl polymer synthesis to afford vinyl polymers having a certain domain of polyrotaxane crosslinking points (Figure 14) [84]. In this system, the crosslinker was

• synthesized and exhibited a rotaxane crosslinking nature; hence, the resulting vinyl polymer, e.g., polyDMAAm crosslinked by VSC, showed enhanced stretchability induced by rotaxane crosslinking. Moreover, when it was applied to a thermo-responsive polymer like poly(N-isopropyl acrylamide) (NIPAM), the thermo

• -responsive nature became much faster than the system without VSC. This fast responsiveness was induced by the dynamic rotaxane crosslinking structure. This method can be applied in various vinyl polymer systems, and induces the rotaxane crosslinking nature to the resulting network polymer, suggesting its

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• configuration of the double bond was confirmed using 1H,1H-NOESY spectroscopy. As shown in Figure 2, a correlation between protons of the allyl moiety and the aryl substituent evidenced their spatial proximity in molecule 1c. The absence of a correlation between allyl and vinyl protons additionally supported

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• , C–C bond formation was reported by Chen and colleagues in 2020 via the arylation of vinyl pinacol boronates 23 by using diaryliodonium salts 16 to yield trans-arylvinylboronates 24 in the absence of a metal catalyst [62]. The optimized reaction conditions involve the reaction of substituted

• diaryliodonium salts 16 with different substituted vinyl pinacol boronates 23 in dichloromethane as solvent at 100 °C in a sealed tube in the presence of a wet inorganic base (Scheme 8). Both K2CO3 and Li2CO3 were found to be compatible with the reaction, and it was observed that no product was obtained in the

• , including di- and trisubstituted ones, were well tolerated in the reaction, providing products 24 with good stereoselectivity in moderate to good yields. Moreover, the reaction was successfully conducted with various substituted vinyl pinacol boronates and di(4-tolyl)iodonium triflate, resulting in moderate

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• phenacyl group, yielding 9 without any detectable cyclization product (Scheme 4). This hydration process is thought to proceed via two paths. The reaction is initiated by the protonation of the ethynyl group to generate the vinyl cation intermediate 10. Product 9 is directly formed by the attack of a water

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

• substitution has emerged as a new and robust approach to achieve formal allylic substitution using stabilized nucleophiles. The copper acetylide-bonded allylic cation with copper vinyl allenylidene species as its resonance structure is key for the process, which can achieve the outer-sphere attack of

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• development of a dual-reactive fluorine-containing C2-unit, which was prepared from trifluoroethanol in two steps in 63% yield, allowed the convergent synthesis of fluoroalkenes (Scheme 1C) [26]. We recently found multihalogenated vinyl ethers 1 could be obtained by the reaction of phenols with 2-bromo-2

• First, we optimized the conditions of the Suzuki–Miyaura cross-coupling in reference to the report by Yang et al. (Table 1) [43]. Upon the treatment of multihalogenated vinyl ether 1a with phenylboronic acid 4a (1.3 equiv) and palladium diacetate (10 mol %) as a catalyst at 40 °C, Suzuki–Miyaura cross

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

• agrochemical and pharmaceutical chemistry. In 2019, Jiao and colleagues reported that 1,2-dichloroethane (DCE) could be used as a chlorination reagent for the production of (hetero)aryl chlorides and vinyl chlorides [21]. The reactions were carried out in an undivided cell containing a mixture of DCE in

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• excellent enantioselectivities (89–98% ee) and low to moderate yields (48–72%). The homologation step proceeds via the stereoretentive 1,2-migration of the vinyl group from the tetracoordinated boron to the highly electrophilic carbon of the diazomethane, concerted with the elimination of the nitrogen

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• observed when AQ-3 was applied. Besides, the modifications of the quinuclidine ring through replacing the vinyl substituent in the parent quinine core by a triple bond (AQ-5) led to no substantial improvement in the mixer mill, but the decrease of enantioselectivity in the reaction performed in the

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• the use of HF or its complexes as a reagent. These reactions seem to proceed via the formation of the vinyl fluoride as the intermediate [25][26][27][28]. In the first example, Olah and co-workers reported the reaction of terminal alkynes with HF/pyridine (Olah reagent) (Figure 1, reaction 1) [29][30

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• the strain-promoted double azide addition feature, DBA 5 was evaluated as a crosslinker for azidated polymers. After 5 (5 mol %) was added to a partially azidated poly(vinyl chloride) (PVC-N3) (x = 0.11, n = 1000) in THF, the solvent was gradually evaporated on a Teflon boat. The resulting self

• metal-free click reaction was employed to crosslink a partially azidated poly(vinyl chloride). The crosslinking proceeded by simply mixing the polymer and crosslinker in THF and evaporating, and the formation of the crosslinked polymer film was confirmed by the strain–stress curves. The developed method

• partially azidated poly(vinyl chloride) (PVA-N3) was prepared by stirring poly(vinyl chloride) and NaN3 in DMF at room temperature overnight. Measurements NMR spectra were recorded using a JEOL mode Al300 (300 MHz) at room temperature. Deuterated chloroform was used as the solvent unless otherwise stated