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

• behavior, enabling the translation of the macrocycle along the axle upon irradiation with light (Figure 3) [21]. Anthracene Anthracene undergoes [4π + 4π] dimerization upon irradiation with light, whereas cycloreversion is achieved thermally (Figure 2) [27]. Tron and co-workers synthesized a [2]rotaxane

• composed of a dibenzo-24-crown-8 (DB24C8) and an axle with anthracenes as stoppers on both ends [28]. Light irradiation at 365 nm triggered the dimerization of the anthracenes allowing the conversion of the [2]rotaxane into a [2]catenane. Cycloreversion and formation of the rotaxane was achieved thermally

• composed of a large crown ether macrocycle containing two anthracene moieties and an axle consisting of dibenzylammonium hexafluorophosphate [83]. Light-induced anthracene dimerization reduces the macrocycle’s cavity, strengthening its interaction with the axle. As a result, the initially rapid dethreading

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• produce 11, which could be further converted to 12 and 13 for an intermolecular Mannich-type dimerization to form the C2–C3’ linkage [13]. Further oxidation state adjustment would give complanadines A, B, D, and E. Since their isolation, the complanadines, especially complanadine A, have attracted a

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

• ). Partial γ-acyloxy-Cy7 possesses a high fluorescence quantum yield and high photothermal conversion efficiency in PBS, two pivotal parameters in fluorescence imaging and image-guided photothermal therapy [196]. A dimerization of furfural has been found to occur at the early stage of formation of humins

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• for the asymmetric synthesis of saddle-shaped inherently chiral dibenzo[b,f][1,5]diazocines 72 via CPA catalysis [55]. In the presence of CPA 7 (10 mol %) and the corresponding 2-acylaniline 73 (20 mol %) as co-catalysts, the asymmetric dimerization of 2-acylbenzo isocyanates 71 allowed access to

• chiral DDDs via CPA-catalyzed cyclocondensation. Asymmetric synthesis of saddle-shaped inherently chiral 9,10-dihydrotribenzoazocines via CPA-catalyzed (dynamic) kinetic resolution. Enantioselective synthesis of inherently chiral saddle-shaped dibenzo[b,f][1,5]diazocines via CPA-catalyzed dimerization of

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• other, as illustrated by the electrostatic potential in Figure 2. This unique structural feature facilitates molecular stacking, wherein the negative region of one molecule interacts with the positive region of another. Dimerization of 1.2.3-c.c. is thermodynamically (ΔH0) favored – the dimer is 3.8

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• tested also did not promote the reaction between 1 and 2a, but some of them were found to catalyze the dimerization of azirine 2a to 2H-imidazole 4 (Table 1, entries 6‒9). Imidazole 4 is a known compound that is formed in low yield upon treatment of azirine 2a with FeCl2 in MeCN [20]. To our delight, the

• formation of the C–C bond between the rings of the reacting molecules occurs in the coordination metal sphere as an intra-, rather than intermolecular, process. The formation of compound 17, the product of oxidative dimerization of indole-based enol 15, in the second reaction also points to different

• mechanisms of the formation of azirindine 16 under Ni(II)- and Cu(I)-catalysis. Oxidative dimerization of non-aromatic cyclic enols has been previously observed in their reactions with 3-arylazirines catalyzed by Cu(I) and Cu(II) complexes and was attributed to the recombination of intermediate free radicals

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• of nitrile oxides to isocyanates or their dimerization [26][27]. Since isomerization is believed to be the primary direction of molecule degradation only for bulky o,o'-disubstituted aromatic dipoles [28][29][30], the main efforts in developing a methodology were focused on suppressing dimerization

• was employed. The substantial impact of the reaction conditions can be attributed to the stability of the dipole formed. The presence of mesomeric donor substituent (such as 4-OMe group) has been shown to render nitrile oxides more susceptible to dimerization in comparison to other dipoles [27][34

• this case, the strong electron-withdrawing properties of the carboxyethyl group in CEFNO can significantly inhibit the reaction with 2f, lowering the energy of the HOMOdipole involved in the interaction. Instead, the reaction can proceed towards dipole dimerization [37], which is generally much easier

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• isolated quickly and in good yield, without the need for time-consuming purification steps. At the same time, no cumbersome precautions, such as an inert atmosphere, are necessary. Another fantastic Letter was contributed by Fañanás-Mastral and co-workers, in which a rare copper-catalyzed dimerization

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

• decarboxylation was induced by a photochemical oxidation using an iridium catalyst, and the resulting benzylic radicals were coupled with activated alkenes through a Giese addition which was irreversible due to the strained nature of the starting radicals. As a result, radical dimerization was minimal and the 3,3

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• CHCl3, AcOH and o-DCB [44]. The resulting mixture of brominated PAHs 30 and 31 was then subjected to single or double [3 + 2] annulation with various alkynes, leading to the extended structures 32 and 33. Notably, compound 33d can undergo Pd-catalysed dimerization, resulting in the formation of a chiral

• dimerization of alkynes, followed by the expansion of a phenyl ring leading to the formation of an azulene moiety, was first reported over half a century ago. These reactions can be carried out using various catalytic systems, including sulfenyl chloride/AlCl3 [50], palladium catalysts [51] or gold catalysts

• resulted in the mixture of isomeric π-extended azulenes 51 and 52 in rather moderate yields of 8% and 8%, respectively. Both PAHs 51 and 52 contain also embedded non-alternant indenophenalene subunits. Similarly, Murakami and co-workers reported intramolecular dimerization of alkynes followed by a phenyl

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• triphenylmethyl radical [38][39]. In contrast to the Gomberg radical, the perchlorination prevents dimerization through the para-position. Moreover, the chlorine substituents in the ortho-positions twist the phenyl rings into a propeller conformation and out of the sp2-hybridization plane of the central methine

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• are shown to undergo a rare dimerization process when reacted with bis(pinacolato)diboron under copper catalysis. The reaction provides densely functionalized products with excellent levels of chemo-, regio-, and diastereoselectivity. This high degree of functionalization makes these products

• versatile building blocks for the stereoselective synthesis of chlorocyclopropanes. Keywords: chlorocyclopropanes; copper; cyclization; 4,4-dichloro-2-butenoic acid derivatives; dimerization; Introduction In the last years our group has been focused on the development of catalytic methodologies for the

• transformation could be efficiently applied to the dimerization of other 4,4-dichloro-2-butenoates and 4,4-dichloro-2-butenamides. The corresponding products 8 and 9 were obtained in good yield and excellent diastereoselectivity (Scheme 2). In sharp contrast, the use of gem-dichlorides bearing a ketone group did

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• crystallography, was irradiated, resulting in Cl2B (C), which showed approximately 18% dimer formation, while no dimerization was observed in the Me2B and Me4B (C) samples (see experimental section for details). The initial presence of the [2 + 2] dimer in the Cl2B (A) sample can be attributed to improper

• shielding from light, and unavoidable light exposure during crystal selection, and the X-ray measurement itself. As an additional test, the compounds were prepared as NMR samples in DMSO-d6 and irradiated with 405 nm LED. Irradiation in the solution phase did not result in any dimerization; the respective

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

• adhesion on the vial walls. Thus, the reactor was operated at 17.7 Hz for 20 h and the dimerization to 9.2 occurred in 96% 1H NMR yield with a 6:94 anti/syn selectivity. A different selectivity was observed when crystals were first ground, and then irradiated under argon without applying forces (65% yield

• ://creativecommons.org/licenses/by/4.0). Photomechanochemical control over stereoselectivity in the [2 + 2] dimerization of acenaphthylene. The photo in Scheme 9 was republished with permission of The Royal Society of Chemistry, from [75] (“Photomechanochemical control over stereoselectivity in the [2 + 2

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• Bingnan Wang Yong Lu Chuo Chen Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA 10.3762/bjoc.21.28 Abstract Chemically induced dimerization is a powerful tool for studying protein function, wherein the IMiD (the “immunomodulatory

• contamination. Keywords: glutarimide; IMiD; impurity; nucleophilic acyl substitution; PROTAC; Introduction Targeted protein degradation capitalizing on the concept of chemically induced dimerization has emerged as a new therapeutic approach recently [1]. In particular, the modularity of proteolysis targeting

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• . Diverse functionalized 3-substituted oxindole derivatives were successfully prepared in satisfactory yields and with high diastereoselectivity. In addition, the base-promoted dimerization of MBH carbonates of isatin afforded the ethylene-bridged bis(3-methylene)oxindole derivatives with nearly 4:1

• diastereomeric ratios. The relative configurations of the various polycyclic compounds were clearly elucidated by determination of several single crystal structures. Keywords: allylic SN2 reaction; dimerization; isatin; MBH carbonate; 3-methyleneoxindole; Introduction Isatins (indoline-2,3-diones) possessing

• have been obtained by DABCO-catalyzed dimerization of MBH carbonates of isatin in ODCB at high temperature (150 °C), which could be converted to bisspirooxindole derivatives via the isomerization of the double bond and a sequential thermal 6π-electrocyclic ring-closure process [30]. Here, the novel

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• pentacenes, are relatively stable molecules under ambient conditions, longer acenes undergo spontaneous dimerization and react with oxygen [5][6], owing to the rising diradical character. This behavior was also observed in the oxidized species of shorter acenes [7]. Surprisingly, Bettinger and Einholz [5

• ] reported a stable heptacene dication in concentrated sulfuric acid, a stability attributed to the intermolecular Coulomb repulsion between the charged molecules, which prevents the dimerization of the acene. This exciting finding suggests possible modes of kinetic stabilization of oxidized species of π

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

• not give the product, suggesting that conversion of sodium 4-methylbenzenesulfinate to 4-methylbenzenesulfinic acid was required. Several solvents were tested and found to produce the disulfide in low yield (Table 1, entries 6–11), except for dimethylacetamide (DMA). Given the dimerization nature of

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• covalently linked polymers. So far, the design of such monomers has relied heavily on three-dimensional macrocycles, and the use of two-dimensional shape-persistent macrocycles for this purpose remains rather rare. Here, we demonstrate a dimerization motif based on a hydrogen-bonded macrocycle that can be

• polymerization concentration of 17 μM. These polymers were highly concentration-dependent. Establishing this new dimerization motif with shape-persistent H-bonded macrocycles widens the scope of noncovalent building blocks for supramolecular polymers and augurs well for the future development of functional

• capable of dimerization by binding to a macrocycle in a 2:2 stoichiometry [22][23]. Such binding motifs are intriguing for macrocycle-mediated supramolecular dimerization since they may enable multiple modes of noncovalent connectivity through combination with other noninterfering interactions (e.g

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

• reactions, particularly in controlling the high reactivity and selectivity of radical intermediates [13][14]. Early studies on copper-mediated radical reactions, such as Julia’s work on radical cyclization reaction [15], along with advancements in dimerization [16][17], oxidative cleavage [18][19], and

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

• four-step process involves allylation, Claisen rearrangement, isomerization, and oxidative dimerization. Each reaction step was optimized independently by using either online HPLC or in-line benchtop NMR spectroscopy to afford an overall yield of 67% in 66 iterative experiments over four linear

• convenient methodology for global optimization, eliminating the necessity of a theoretical model. A reconfigurable automated flow platform integrating online HPLC monitoring was used for the cobalt-catalyzed aerobic oxidative dimerization of desmethoxycarpacine (6) to carpanone (7) in the presence of oxygen

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

• in the medicinal chemistry arena, in stark contrast to single BCP units over the past 12 years [20][21][22][23][24]. One plausible explanation for the paucity of applications of [n]staffanes in materials or biological settings is a synthetic accessibility issue. For instance, dimerization of

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

• final peroxide 157: recombination of radical C with tert-butylperoxy radical D or oxidation of radical C to carbocation E, which is nucleophilically attacked by TBHP. β-Peroxy ketones 159 were synthesized via oxidative dimerization of styrenes 158 using the Cu(I)/TBHP system (Scheme 50) [42]. The

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• material in Europe (Scheme 1). It is obtained by extraction and isolation of the colorless indole-O-glycoside indicane which is then hydrolyzed to give indoxyl. The latter undergoes oxidative dimerization to provide indigo. In the 19th century, syntheses of indigo were developed which made the pigment

• precursors. The base-mediated reaction of 5-chloroanthranilic acid (8a) with chloroacetic acid afforded 8b (Scheme 5) [20]. Acetylation and base-mediated cyclization gave indoxyl 9a which was transformed to indigo 1c by oxidative dimerization. Benzylation finally afforded 1d. 4,6-Benzylidenation of ᴅ

• ‘-diglycosides In our group, the synthesis of N,N’-diglycosylated isoindigos was studied. In contrast to isatin-N-glycosides, oxindole-N-glycosides are not readily available. Therefore, reductive dimerization of isatin-N-glycosides was considered as a strategy for the synthesis of the target compounds. Isatin-N