Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• decision-making [6][7]. Antibody–oligonucleotide conjugates, antibody–enzyme conjugates, antibody–polymer conjugates, antibody–nanomaterial conjugates, antibody–catalyst conjugates, and antibodies involved in protein degradation also play critical roles in biomedical research and therapies [2]. In whatever

• transformations is a strong electrophile that can react with Tyr, for instance, if such an amino acid is located near the reactive site. In addition, command of the DAR might have some limits, as the distance between the catalyst and the mAbs is not well defined, meaning that the photoredox reaction might not

• available and inexpensive Ru(bpy)3, along with a water-soluble, air- and moisture-stable Ni(dabpy)Br2 catalyst. Moreover, they demonstrated that this system works efficiently in aqueous conditions, making it highly suitable for applications involving antibodies. These characteristics make the method highly

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• ] with which a wide range of aromatic and aliphatic disubstituted alkynes were reactive, resulting in a greater diversity of quinolines II. In both cases, regardless of the catalyst used, the MCR tolerates a wide variety of anilines that have either electron-donating or electron-withdrawing groups with

• derivatives are isolated as side-products. Interestingly, when Liu et al. [40] modified this reaction by using a copper(II) catalyst under aerobic oxidative conditions, the regioisomers III (2-arylquinolines) were obtained (Scheme 9). To rationalize this singular result, the authors proposed a mechanism in

• DMSO (Scheme 12) [45]. In this case, the reaction works well under metal-free conditions using iodine as the catalyst. Remarkably, the activation of DMSO was accomplished using Selectfluor, and in this case, DMSO is the source of a C-1 unit. It is important to note that the reaction could be performed

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• catalysis (Figure 2c). Results and Discussion Chiral halonium salts 9a–c were prepared according to our previously reported methods [33]. The Mannich reaction of ketimine 7a and cyanoester 16a was selected as a benchmark, and catalyst screening was conducted (Scheme 1). The reaction was carried out with 1.0

• product was obtained in moderate diastereo- and enantioselectivity, however, chloronium salt 9c did not show significant catalytic activity, and the product was formed in nearly the same yield as that obtained without a catalyst with low stereoselectivity. From these observations, bromonium salt 9a was

• , the reaction catalyzed by only 1 mol % of iodonium salt 9b provided the opposite diastereomer of 17a as the major product compared with that without a catalyst, which revealed the high catalytic activity of our catalyst. Further reaction conditions optimization was conducted using 9a as a catalyst

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• [32]. Then, we increased the reaction scale to 0.2 mmol and obtained similar results (Table 1, entry 13). At this point, we decided to explore the use of a bifunctional organocatalyst in order to improve the yield. When squaramide SQ-1 was used as a catalyst, we observed a similar yield and

• diastereoselectivity after 24 h of reaction (61% yield and 7:1 dr, Table 1, entry 14). By lowering the reaction temperature to 50 °C using the same catalyst (Table 1, entry 15), the yield of the reaction increased slightly to 73% in 24 hours. Disappointingly, the bifunctional thiourea THIO-1 gave a lower yield and

• . Considering the high diastereoselectivity observed both in the presence and absence of the squaramide catalyst, we propose a plausible mechanism (Scheme 3) that involves hydrogen bonding activation of the methyl trifluoropyruvate by the NH₂ group of the aminopyrazole. This interaction directs the attack of

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• , HOAt, N,N-dimethylformamide 0 °C for 2 h and at rt for 20 min, 11%; f) Grubbs II catalyst, CH2Cl2, reflux, 3 h, 84%; g) TFA, H2O, CH2Cl2, 0 °C to rt, 5 h, 91%. EDC·HCl = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; DMAP = 4-(dimethylamino)pyridine; TFA = trifluoroacetic acid; HOAt = 1

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

• [23]. Nevertheless, the arylation of monohalogenated N-acetyl diazocines via Stille coupling in our case gave unsatisfying results (Table 2). Reactions with tetrakis(triphenylphosphine)palladium(0) as catalyst resulted in no product 7 formation. Bis(tri-tert-butylphosphine)palladium(0) as catalyst

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting

• chromatography [1]. Sometime later, kinetic resolution (KR) emerged. This method is based on the different reaction rates of each enantiomer in a racemic mixture when they are reacted with a reagent, a chiral catalyst, or an enzyme. This process results in obtaining the less reactive enantioenriched enantiomer

• processes with low catalyst loading. It involves the kinetic resolution of alcohols, amines, and esters using chiral phosphoric acids [6][7][8][9][10][11][12][13] and sulfoximines with enals using chiral N-heterocyclic carbene (NHC) catalysts [14]. Additionally, these processes have been conducted using

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

• % yield, albeit after 72 h of irradiation. This experiment proved that 4.2 can be used in a sub-stoichiometric way, in fact acting as a catalyst. More recently, based on their previous approach via manual grinding (Scheme 2) [64], MacGillivray and co-workers adopted the vortex grinding method to enable

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• polarization (enthalpic) (Figure 1). Organization, the control of the position(s) and orientation(s) of reacting molecules, has been achieved historically in supramolecular chemistry using “pre-organized” catalyst designs (vide infra). More recently, organization has been mooted by List as a unifying concept

• across many fields of selective catalysis under the term confinement [3], a term borrowed from heterogeneous catalysis. Polarization can be understood as the catalyst providing an electrostatic environment that works to stabilize electron redistribution. Since all reactions redistribute electrons, and

• work simply by bringing substrates arbitrarily close to a potentially reactive group [99][100]. One rare but important exception is Breslow’s use of two tethered cyclodextrins to locate hydrophobic ester substrates next to a metal ion. Breslow’s catalyst accelerates the hydrolysis of esters and

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• sections. Similarly, Pertel and co-workers also demonstrated the use of 2-(2,2,2-trichloroethoxy)-2-oxazoline glycosyl donor 22 (Scheme 4) which could be used for stereo- and regioselective glycosylations using extremely mild conditions [94] and requiring low concentrations of the catalyst. In this case

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• ]. In addition, we have previously demonstrated the effective use of alkyl 3-bromo-3-nitroacrylates in the preparation of condensed furancarboxylates using potassium acetate as a catalyst [28][29][30]. The present study is aimed at developing methods for the synthesis of a wide range of condensed

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

• diverse catalyst types and applications. The first section is dedicated to metal-based photocatalysts. Complexes involving metals such as osmium and ruthenium, have dominated red-light photoredox catalysis because of their ability to absorb low-energy photons and sustain redox cycles via stable excited

• of side reactions. This latter advantage has been notably exploited in the case of ring-closing olefin metathesis reactions, where Weizmann et al. utilized the photothermal response of plasmons from gold nanoparticles to activate the catalyst [17]. This approach contrasts with the work of Rovis et al

• in continuous-flow conditions. This performance is particularly notable given that the reaction was carried out using sub-part-per-million loadings of the catalyst (0.003 mol %), a stark contrast to traditional systems, which often require higher concentrations of heavy metals. Unlike classical

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• characteristic triplets at 5.76 and 2.77 ppm (J = 7.0 Hz). Compound 3 was also formed in almost quantitative yield in acetonitrile within one day in the presence of ʟ-proline (Table 1, entry 10), which is an effective catalyst for crotonic condensation [22]. Since the reaction of diketone 1 in the presence and

• an important role; the presence of the condensation catalyst ʟ-proline accelerated the absorption of formaldehyde vapors by the reaction mixture. Carrying out the same reaction in the absence of a catalyst in CDCl3 and subsequent 1H NMR spectroscopy analysis showed that the mixture contained 42% of

• adducts of the Diels–Alder (i.e., I) and the hetero-Diels–Alder reaction (i.e., II), or adducts resulting from the addition of a second equivalent of CH acid to the crotonic condensation product (i.e., III). Apparently ʟ-proline played an essential role as catalyst in this three-component reaction. Using

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

• -toluenesulfinate as the model substrate and tetrabutylammonium iodide (TBAI) as the catalyst, the results are listed in Table 1. Various acids were tested to assess their effect on the reaction (Table 1, entries 1–5). From the results, it could be concluded that, in the presence of strong acids, all afforded the

• been further decreased, in the end, 0.5 mL of DMF was used because of the solubility of the reagents. Increasing the amount of catalyst to 20 mol % resulted in a significant increase in the yield, but further increases did not significantly change the yield (Table 1, entries 14 and 15). A decrease in

• reaction temperature resulted in a significant decrease in the yield (Table 1, entry 16) and at 80 °C no desired product, but only thiosulfonate was formed (Table 1, entry 17). The reaction did not proceed in the absence of acid or catalyst (Table 1, entries 18 and 19). Compared to TBAI, other iodized

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• CF2HCO2H or PhCF2COOH, along with benzimidazoles bearing unactivated alkenes and PhI(OAc)2 as substrates, and proceeded without the need of any base, metal catalyst, photocatalyst or additive. In total, 24 examples were examined, and all of them successfully underwent cyclization reaction to produce the

• with CF2HCOOH or PhCF2COOH, and PIDA under additive-, base-, and metal catalyst-free conditions (Scheme 1b). Results and Discussion Initially, 1-(pent-4-en-1-yl)-1H-benzo[d]imidazole (1a), CF2HCOOH, and PIDA were chosen as the template substrates for this radical difluoromethylation and cyclization

• tricyclic and bicyclic imidazoles under additive-, base-, and metal catalyst-free conditions utilizing difluoroacetic acid and α,α-difluorobenzeneacetic acid as the readily available fluorine sources. The significant advantages of this approach, including its environmental friendliness and cost

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

• , the Chang group elegantly unveiled a protocol for an enantioselective C–N bond formation, introducing δ-lactams from dioxazolones using a copper(I) catalyst and a chiral BOX ligand [74]. As shown in Scheme 2, dioxazolones containing aryl and heteroaryl groups were converted into the corresponding

• ) nitrenoid intermediate INT-7. Subsequent nitrene insertion, protodemetalation, and intramolecular cyclization furnish the desired 1,2,4-triazole. 1.3 Three-component formation of N-acyl amidines In 2019, N-acyl amidines were prepared from dioxazolones using a copper catalyst with terminal alkynes and

• dioxazolone bearing a phenyl group showed no reactivity toward benzoyl amidine under the optimized reaction conditions. Instead, the authors employed a less bulky copper iodide catalyst in the absence of phosphine, successfully affording aryloyl amidine 10f. Furthermore, the electron-rich ethynylanisole

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

• through oxidative addition, followed by transmetalation and reductive elimination, to obtain the desired product. Throughout the catalytic cycle, the catalyst undergoes conversion between [M]n and [M]n+2 (Figure 1) [11]. However, using alkyl electrophiles as coupling partners in cross-coupling reactions

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

• electron transfer to the metal catalyst without the need for chemical redox agents, thus providing milder and more sustainable reaction conditions (Figure 2) [32]. Electrochemical reactions can be performed at low potentials, thereby suppressing side reactions, and chemoselectivity and reactivity can be

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• catalyst, PCy3 (20 mol %) as a ligand, and K2CO3 (2.0 equiv) as a base, the desired arylated naphthofuran 3bb was obtained in 75% yield (Table 1, entry 1). Reducing the reaction temperature improved the yield of 3bb, reaching a quantitative yield when the reaction was performed at room temperature (Table 1

• , entry 3). Reducing the catalyst loading to 5 mol % slightly affected the yield of 3bb, which was 90% (Table 1, entry 4). Next, we evaluated various additives with 5 mol % of Ni(cod)2 to stabilize regenerated zero-valent nickel species (Table 1, entries 5–8). While phosphine ligands such as triphenyl

• optimized the coupling reaction using potassium phosphate as a base and increasing the nickel catalyst loading to 20 mol %, achieving a yield of 78% for the desired product 3bg. When 2-naphthylboronic acid (2i) was employed, its solubility was enhanced using a mixed solvent system of toluene, methanol, and

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

• dual activity as a metal catalyst as well as a Lewis acid [8][9][10][11]. However, in many cases, the role of copper is not clear and both activities often work synergistically. In all other cases, copper’s activity is due to the coordination/complexation with unsaturated systems, but it is rarely

• possible to exclude its action also as Lewis acid. Confirming this dual activity, it should be noted that copper triflate can rarely be replaced by other copper salts or complexes to obtain the same results. In general, catalyst switching does not work with copper triflate, thus supporting its unique

• behavior or reactivity properties. The ambiguity related to the role of Cu(OTf)2 is particularly relevant for cycloaddition reactions, where it is even more difficult to justify the activation of the copper species as a Lewis acid or metal catalyst [12][13][14]. The reaction mechanism involved can be ionic

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

• organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• privileged catalyst frameworks [2]. Axially chiral biaryls have also been found to be useful in materials [3]. Although much less widely occurring than centrochiral compounds, there are also naturally occurring axially chiral compounds. Axially chiral compounds are becoming increasingly relevant also in drug

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ), and appetite suppressants (e.g., phentermine) [6]. Phenethylamines can be produced via numerous different procedures [7]. One of the oldest methods involves the reduction of benzyl cyanide with H2 in liquid ammonia with Raney-Nickel catalyst at 130 °C, and high pressure [8]. Another known method is

• limited, since a NaBH4/transition metal salt system is mostly used to reduce nitroarenes [23][24][25][26]. One of the reported methods takes advantage of titanium(IV) isopropoxide as a catalyst to prepare varied β-phenethylamine analogues. Despite its simplicity, the reaction time is quite prolonged (from

• ]. Consistently, once the chloride is added, the reduction to free Cu(0) is visually indicated by the immediate disappearance of the blue color of the copper(II) solution, and the formation of a fine suspended black powder. The latter, as metallic copper particles, acts as the actual catalyst. Time plays a

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

• literature in other areas relevant to the application of ML to chemical synthesis that are not covered by our review, such as small molecule discovery [8], drug discovery [9][10], retrosynthesis [11][12], and catalyst selection and design [13][14]. Review HTE platforms HTE platforms were designed to

• light [40]. The design allows the screening to be more material- and time-efficient in the optimization of both continuous variables (e.g., temperature and residence time) and discrete variables (e.g., catalyst, base). Pieber et al. [46] reported the application of a segmental flow reactor for

• -flow pattern using a Y-shaped mixer, followed by the suspension of the catalyst via a T-mixer. This technology was utilized to develop selective and efficient decarboxylative fluorination reactions. Recently, a slug flow platform was developed (Figure 3a) by injecting segments of gas as a separating

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• of chemistry as being a catalyst to more than a century of glycobiology, with a profound and exciting vision for the future. Elisa Fadda, Rachel Hevey, Benjamin Schumann and Ulrika Westerlind Southampton, Basel, London, Umeå, November 2024

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• , TADF emitters containing the PhFlOP unit as an electron acceptor are still scarce. Meanwhile, the syntheses of the TADF emitters by the groups of Nishida and Wu both utilized palladium noble metal as a catalyst [31][32][33]. Therefore, it is of great significance to develop cost-effective synthetic

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• )Cl2·CH2Cl2 was used with 5 mol % catalyst loading (Table 1, entry 1). Next, we examined whether different thiophene-3-ylboronic esters could also be used under the same reaction conditions. A variety of borylation methods are capable of providing different boronic esters, such as pinacol [44][45][46