Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• , and control reactions support sensitization, enabling an intramolecular [2 + 2] cycloaddition to be realized accessing 3D bicyclic fragments containing a boron handle. Keywords: boron; catalysis; [2 + 2] cycloaddition; energy transfer; photochemistry; Introduction The strategic use of a photon to

• identify a suitable catalyst and boron residue, while control reactions and mechanistic studies support the proposed sensitization. The platform enables direct access to mono- and vicinal cyclobutylboronic esters that could be effectively derivatized to demonstrate their potential in synthesis. Results and

• solvent had a profound effect on reactivity with more Lewis-basic solvents suppressing reactivity (Table 1, entries 4 and 5 vs entries 6 and 7), indicating p-orbital availability plays a prominent role [56][57]. A control reaction (Table 1, entry 8), in combination with UV–vis absorption studies (see

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• that a tripodal hexaurea receptor L (Figure 1b) could selectively and reversibly extract sulfate and phosphate anions from water into organic phase (under pH control) [30][31][32][33]. Single crystal structures of the receptor–K2SO4 complex in the presence of 18-crown-6 clearly displayed ion-dipole

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• 96% isolated yield (Table 1, entry 12). Control experiments indicated poor results when no catalyst was used, with the corresponding product obtained only in 31% yield (Table 1, entry 13). When CuI or chitosan alone was used as a catalyst, the reaction occurred but with less efficiency (Table 1

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• are molecules reversibly changing their optical and chemical properties upon irradiation. These features offer easy, precise, and reversible control over the system they are embedded in and make them attractive modulators for diverse applications. In the last decades, many classes of photoswitches

• -art technologies ranging from energy-storage materials [6][7] to pharmacology [8][9][10][11], materials chemistry [12][13], control of peptides structure [14][15] or proteins [16], as antibacterial agents [17][18], smart coating [19], or multivalent photoresponsive systems [20][21], to name only a few

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• ligands (Figure 4 and Figure 5). Additionally, dexamethasone (DEX) was employed as an experimental control for comparative purposes [34][35][36]. The docking scores (DS), reported in Table 5 as binding affinities, reveal that negative DS values correspond to stronger binding affinities between the ligand

• ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown as red dashed line. The bioavailability radar of studied compounds 5a–e. The interactions of potential drugs 5a–c in the active site of enzyme iNOS. The interactions of potential drugs 5d and 5e and control drug (DEX) in the

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

• examined in the presence of TEMPO as a radical scavenger, and the results revealed that the reaction proceeded through a radical pathway. The results of control experiments suggested that the phosphorylation might proceed through ferrocenium. It should also be noted that ferrocene and ruthenocene compounds

• reaction was carried out in an undivided cell using platinum electrodes as the anode and cathode. In this method, S8 was used as a sulfur source and ammonium iodide as a mediator, which has a key role. Based on the control experiments, a nucleophilic substitution is the main pathway for the reaction. The

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• kcal·mol−1 higher in energy, resulting in a theoretical ee value of 74% (at 263 K), if pure Z-hydrazone would be used and under the assumption of kinetic reaction control. In contrast, the E-hydrazone gives preferably the "R" product (with a theoretical ee value of 64%). The transition state which gives

• -hydrazones, respectively. A thermodynamic control of the reaction outcome (i.e., especially enantioselectivity) would require the possibility to approach an equilibrium between 9 and 10 (seeing the reversibility of step 9 → 10), in which case the relative energies of stereoisomeric forms of 10 determine the

• of the relative stabilities of different forms of this complex. Consequently, under kinetic reaction control, enantioselectivity would decrease over time as the reaction progresses. This occurs because slower-reacting complexes would accumulate, leading to a gradual equilibration of reaction rates

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• ]. Specifically, the reversible E/Z isomerization of the azo group in azobenzene glycosides is suited to control the spatial presentation of glycoligands and, for example, switch carbohydrate-specific bacterial adhesion on and off [20][21][22][23]. Indeed, glycoazobenzene derivatives are excellent tools to

• like glycoclusters 1 and 2 are capable of many conformational alternatives and therefore, the control of molecular shape by photoisomerization of azobenzene linkers has its limitations. In addition, water solubility requires improvement. Furthermore, our study, combining synthesis, analysis of

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

• % dichloromethane. General procedure D. In a manner similar to [11], the product obtained in general procedure B, methanesulfonyl chloride, and triethylamine were dissolved in dichloromethane and stirred overnight at room temperature. After reaction control and 100% consumption of the starting material, the entire

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• stereoelectronic effects such as hyperconjugation and electrostatic attraction/repulsion. These fluorine-derived conformational effects have been exploited to control the shapes, and thereby enhance the properties, of a wide variety of functional molecules including pharmaceutical agents, liquid crystals

• involve conformational control it is outside the scope of this review. Another way to fluorinate the end of an alkyl chain is with a 1,2-difluoro pattern. The vicinal difluoro motif is able to sample different rotamers (e.g., with the C–F bonds aligned either gauche or anti). Crucially however, such

• emerges. The 1,3-C–F bonds tend to avoid a parallel alignment, due to dipolar repulsion (III, Figure 3) [30][31][32]. This phenomenon can be harnessed to control molecular conformations in a predictable way, and once again the stereochemistry is important. For example, compare the natural product

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

• transmetalation of organolithium and organoboron compounds, copper hydride catalysis, and enantiotopic-group-selective transformations of 1,1-diborylalkanes. Detailed mechanistic insights into stereochemical control and current challenges in this field are also discussed. Keywords: allylic substitution; chiral

• catalysts generally produce straight-chain products lacking chirality when reacting with monosubstituted allylic substrates, whereas iridium catalysts selectively generate branched products with high optical purity and precise control over the reaction site. Furthermore, the development of chiral

• temperature led to a significant decrease in dr values, suggesting partial racemization. This observation highlights the importance of careful experimental handling of [RCu·ZnX2·L] species {X = Br, Cl; L = P(OEt)3}, where both temperature control and reaction time must be precisely managed to maintain

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• monohydrolysis under basic conditions. The electrolysis proceeds in an undivided cell under galvanostatic control using low-cost graphite or stainless-steel electrodes, and the protocol was easily upscaled. Notably, an excellent diastereoselectivity (97:3 dr) could be achieved in the cyclization of a tethered

• relatively narrow potential window of 0.22 V between the desired decarboxylation of 9a (Ep = 1.56 V vs Ag/Ag+) and the undesired Shono-type oxidation of the formed 6a required careful control of the amount of passed charge to afford high yields of 6a. Next, the formation of decarboxylation product 11a was

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

• thus to have a better control of the selectivity and the DAR, leading to more homogeneous ADCs. In this specific context, photocatalysis (Figure 2) enables site-specific bioconjugation by generating reactive intermediates (such as radicals or electron-deficient species) that can selectively react under

• the agency of low-energy visible light with specific functional groups on biomolecules. This allows precise control over the conjugation process, enabling targeted modifications without affecting non-reactive sites. Although previous reviews have discussed the more traditional synthetic methods

• facilitate various modifications, including labeling, crosslinking, and the creation of protein–drug conjugates. The incorporation of photoredox strategies has facilitated the synthesis of complex protein architectures, enabling precise control over conjugation sites and degrees of modification. The number

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• challenge in clinical practice. This resistance often leads to treatment failure and poor survival outcomes for patients [1]. Another ongoing problem is the excessive use of chemical pesticides such as methyl bromide, carbamates, and organophosphates to control plant-parasitic nematodes that has shown a

• added to 120 µL aliquots of a cell suspension (5 × 104 cells/mL) in 96-well microplates. After 5 days incubation, an MTT assay was performed, and the absorbance measured at 590 nm using an ELISA plate reader (Victor). The concentration at which the growth of cells was inhibited to 50% of the control

• (IC50) was obtained from the dose–response curves. Epothilone B was used as the positive control. Nematicidal activity Nematicidal activity was performed using Caenorhabditis elegans in a microtiter plate assay as described by Rupcic et al. (2018) [30]. The assay was performed in four concentrations

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• , successfully forming the aryl-containing quaternary center. However, in this step, the reaction was too rapid to control. After optimizing the reaction time and temperature, the reaction was carried out at −30 °C for 15 minutes and product 14 was isolated in a yield as high as 58% [14]. Iodination of compound

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

• concerns and improved reaction control can be addressed, paving the way for more efficient and sustainable synthetic methodologies. Keywords: cascade reactions; formaldehyde surrogates; green chemistry; heterocycles; multicomponent reactions; Introduction Organic chemistry is a mature discipline that has

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• peptides for binding we prepared the derivatives of peptides 2–4 bearing an acetyl-capped N-terminus (compounds 5–7). As a control we also studied tripeptide 8 containing exclusively alanine residues. The binding of tripeptides was again studied by ITC and fluorescence spectroscopy and the results are

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

• control of equivalents and pH, or Leuckart–Wallach-like reaction with ammonium formate and Pd/C [25] provided monomethylaniline 7 in 37% and 35% yield, respectively. The absolute structure of monomethylaniline 7 was confirmed by single-crystal X-ray diffraction measurements (Figure 2). Compound 7

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• were collected at 100(2) K using a diamond (111) crystal monochromator, a wavelength of 0.41328 Å, and a Bruker CCD detector. The structure was solved using direct methods and refined (on F2, using all data) by a full-matrix, weighted least squares process. Standard Bruker control and integration

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• harmful to human health and this became a significant challenge to food security [6]. Long-term synthetic pesticide applications to control the red flour beetle has resulted in the development of resistance to organophosphates, pyrethroids, methyl carbamates, and neonicotinoids [7][8]. It became critical

• for devising a more effective and environmentally friendly strategy to control this pest [9]. Pheromone-based pest management is one of most environment benign, effective, and promising solutions [10][11]. The aggregation pheromone of T. castaneum was first reported by Ryan in 1976, secreted by the

• tosylate and a chiral Grignard reagent. The synthetic pheromone could be valuable for the control of the red flour beetle. The aggregation pheromone of Tribolium castaneum. Retrosynthetic analysis of the aggregation pheromone (4R,8R)-1. Synthesis of chiral tosylate (S)-10. Synthesis of chiral tosylate (R

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

• accumulation in the environment after excretion [1][6][7]. These superior properties of diazocines have been exploited in several applications such as the control of protein folding by implementation as cross-linkers between protein side chains [8] or in peptide backbones [9], as photoswitchable

• efficiency. In any case the light-induced geometry change via isomerization should selectively control the interaction between the inhibitor and the receptor [21]. Currently there is only one example reported in the literature for the incorporation of N-acetyl diazocines into biologically active molecules

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

• the surface area of the solids and, therefore, irradiation efficiency. UV lamps (e.g., medium-pressure Hg lamps) are typically used for irradiation, thus requiring specialized safety equipment. While it offers some control over pressure and duration, manual grinding suffers from inconsistencies due to

• , since in a control experiment without RFTA the mixture was found to liquefy. This was due to the heat generated by LEDs and not by the grinding action. Thus, light irradiation fulfils a double function: the excitation of the photocatalyst and melting of the substrate, inducing mobility of the molecules

• mechanochemistry as well, leading to the introduction of ball milling, which enables precise control over energy input, operating temperatures, and offers the potential for automated, reproducible processes. As an added benefit, the use of closed reactors ensures maximum operational safety, preventing direct

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• substrates that do not form the desired electrochemical oxidation product see Supporting Information File 1, Scheme S1). A series of control experiments was performed to rationalize the observed reactivity trends (Scheme 2). The measured redox potentials EP/2 for 2,2'-dibromo-1,1'-biphenyls 4a–g (from 1.77 V

• the overall oxidation of 4a to 1a likely is a two-electron process, suggesting that the second oxidation step may involve disproportionation of putative Br(II) species (see Scheme 3D). Based on the control experiments described above we propose a plausible mechanism as shown in Scheme 3D. The reaction

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

• a size-selective space [105][126][129][130][132][134]. A key advantage is that these capsules have been made on multi-hundred-gram scales and can be recycled [132]. Additionally, control of structural or bound water by the capsule [105] and properties such as a lowered pKa inside [125] demonstrate a

• instance, the window[1]resorcin[3]arene capsule type [135] demonstrates that the symmetry and properties of traditional symmetric capsules can be modulated, although precise control over the assembly remains difficult. Finally, we must mention the recently reported cavitand capsules of Gibb, who has

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

• by which glutarimide displacement affects quality control analysis, we tested a series of amines and compared the retention times of 8 and 9 (Table 1). Rather surprisingly, the length of amino-PEG-OH had no effect on the relative retention time of 8 and 9. The byproduct co-eluted with the desired