Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• estimated from parameters for enamines (N = 10–16), cyclic N,N-ketene acetals (N = 18–20) [11][12] , and the deoxy-Breslow intermediate (N =15.6) [13]. The nucleophilicity of S,N-ketene acetal 4 clearly exceeds that of ethanol (N = 7.4). In addition, triethylamine is more nucleophilic (N = 17.30 in

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• well with the observed reactivities and selectivity. Attempted macrocyclization leading to linear polymers Formyl groups have diverse reactivities and enable facile condensation, dynamic covalent chemistry, and so on. In this work, we tried the synthesis of cyclic oligomers composed of naphthalene

• molecular weights. These results implied that formation of well-defined cyclic oligomers was quite limited. To increase the well-defined species, [4.3.3]_CH2OH was separated into two enantiopure fractions (Supporting Information File 1, Figure S505), one of which was used for the acid-mediated reaction

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• together to form cyclic oligosaccharides. The naturally occurring cyclodextrins, also named native cyclodextrins, have typically six (α-CD), seven (β-CD) or eight (γ-CD) ᴅ-glucose units [26][27]. Their monomers are all linked by α-1,4 glycosidic bonds, which results in a molecular geometry with a shape

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• curcumscribe the small cyclic core represented by blue color. Three carbonyl amides project outward. B) DFT image of 1 displaying the distribution of Mulliken charges on iodine (purple), oxygen (red), and carbon (grey); benzyl groups are ommited for clarity. C) Calculated electrostatic potential map showing

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• and co-workers (2021) utilized oxime chloride and cinnamic acid to synthesize O-acylhydroxamate 68 in good yield (Scheme 23A) [57]. In the presence of a base, oxime chloride was converted to electrophilic nitrile oxide 69 and reacted with carboxylic acid to form the cyclic intermediate 70. On the

• bond of cyclopropenone to give a cyclic intermediate 316 (Scheme 74A) [125]. On the other hand, Wu and co-workers (2022) developed a Pd-catalyzed selective ring-opening of cyclopropenones and vinyl epoxide 318 to give the corresponding esters 319–321 in good yields via a π–allyl palladium intermediate

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• biocompatibility. The electrochemical properties of such materials have been then evaluated by cyclic voltammetry (CV). For all the properties mentioned above, CDs emerged as low-cost and sustainable photocatalysts. Indeed, upon visible-light irradiation, the generated excited state CD* can operate as either

• four different CDs from citric acid and from blackberries with triarylsulfonium salts. A diffusional rate value was found for all examined nanomaterials (Table 3), pointing to an efficient interaction between the photoexcited CDs and 1b. Cyclic voltammetry experiments have been carried out on both CDs

• product was detected. Conclusion The results arising from cyclic voltammetry analyses, along with the Stern–Volmer fluorescence quenching data and with the isolated products and the GC yields obtained when irradiating the carbon dots in the presence of triarylsulfonium salts, indicate that carbon dots are

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

• oxidation, the Meinwald rearrangement/aldol reaction gave rise to the bridge cyclic intermediate 35, which can finally be converted into both (−)-fortuneicyclidin A and (−)-fortuneicyclidin B. Polycyclization Cyclization/Pictet–Spengler reaction The hexahydropyrrolo[2,1-a]isoquinoline or tetrahydropyrrolo

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

• utilizing in situ-generated π-allylpalladium complexes to capture strained cyclic allene intermediates (Scheme 4) [22]. By modulating the ligands in the reaction system, two distinct polycyclic scaffolds, 13 or 14, could be synthesized with high selectivity. Mechanistically, the Pd(0) catalyst coordinates

• to substrate 11, followed by oxidative addition and release of carbon dioxide to form the zwitterionic π-allylpalladium intermediate Int-21. Under the reaction conditions, silyl triflate 12 undergoes a fluoride-mediated 1,2-elimination to generate the cyclic allene intermediate Int-22. Through a

• , Koenigs, and co-workers demonstrated solvent-controlled bifurcation in the light-driven reactivity of cyclic diazo imides 41 with thiols 42, unveiling two mechanistically distinct pathways (Scheme 11) [40]. In dichloromethane (DCM), the reaction proceeds via a carbene intermediate, enabling cascade C(sp2

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• metabolism [3][4]; cyclic peptides play critical roles in plant or bacterial defenses and as well as animal hormone signaling [5][6]; cyclic proteins exhibit diverse therapeutic functions [7]; and cyclic nucleotides are essential for molecular cloning and hold potential for disease treatment [8]. In contrast

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

• energy sensitizers, would represent an attractive platform for future reaction design. Here, we disclose the photoactivation of simple alkenylboronic esters established using alkene scrambling as a rapid reaction probe to identify a suitable catalyst and boron motif. Cyclic voltammetry, UV–vis analysis

• detrimental to reactivity leading to substrate degradation. Given the ease of access and enhanced stability of pinacol esters to column chromatography, this motif was advanced for further reaction design. Cyclic voltammetry analysis of 1a indicates that single-electron-transfer processes with the excited

• details). Conclusion In summary, photoactivation of simple alkenylboronic esters was established using alkene scrambling as a rapid reaction probe to determine the catalyst and boron moiety for sensitization. The use of cyclic voltammetry, UV–vis analysis, and control reaction probes support sensitization

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

• that when the reaction was carried out in the presence of TEMPO as a radical scavenger, a side product, TEMPO-P(O)R2, was formed (it was confirmed using high-resolution mass spectrometry). The results revealed that the reaction proceeded in a radical pathway (Scheme 1). Based on the cyclic voltammetry

• gave much better results than a graphite plate. The desired product was likely not formed due to the higher oxidation potential of diethyl phosphonate. Cyclic voltammetry experiments confirmed that Cp2Fe is oxidized first due to its lower oxidation potential than other compounds. Moreover, the reaction

• reaction proceeded via anodic indole oxidation, followed by a reaction with trialkyl phosphite to give the corresponding indole phosphonate (Scheme 11). Cyclic voltammetry experiments confirmed that free indole can oxidize at the anode and generate a radical-cation intermediate. Also, no product was

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

• -state structure, two bonds (Ca–O and Si–C) are broken, while a Si–O bond is simultaneously formed, in a concerted step implying a cyclic flow of six electrons in a five-membered ring. The isocyanide Ca–N–C bond angle in TS 11-12 lies between that of 7 and 9. While the replacement step is slow, and hence

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

• favourable accommodation of a wider C–C(F2)–C angle within the cyclic product 11. Another illustration of the geometric perturbation caused by the wider C–C(F2)–C angle comes from the stearic acids 12 and 13 (Figure 3); the gem-difluorinated analogue 13 has substantially greater conformational disorder

• interruption of the fluorine pattern means that the C–F dipoles no longer all cancel each other out, and this results in a very high calculated molecular dipole (μ = 7.15 D). Having concluded our survey of linear alkanes, we will now focus on cyclic systems [48]. When fluorine is introduced into a small

• pendant aryl moiety, is better for target-binding and hence 41 is a ≈10-fold more potent inhibitor of BACE-1 than 40. Several further examples of cyclic ethers will be examined in section 5 (sugars). The anomeric effect applies in acyclic ethers, too. Consider the non-fluorinated scaffold, Ph–O–CH3 (42

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

• cyclic amino acids are common structural motifs in the design of small-molecule drugs and peptidomimetics [1]. For example, the clinically used anesthetics carfentanil (1) and remifentanil (2), the FDA-approved antipruritic medication defelikefalin (3), and the arginase inhibitor 4 [2] possess cyclic α,α

• -disubstituted piperidine-containing amino acid subunits. Likewise, a cyano-substituted cyclic aminal is a core structural unit of the fibroblast activation protein inhibitor 5 [3] (Figure 1). The widespread use of non-proteinogenic cyclic amino acids in drug discovery justifies both the design of new analogs

• feature at Ep = 1.78 V vs Ag/Ag+ (100 mV/s scan rate; see Figure 3A), and the electrolysis of pyrrolidine 6a under the optimized anodic decarboxylative cyclization conditions (entry 8, Table 1) afforded cyclic hemiaminal 12a (33% NMR yield), whose structure was proved by NMR experiments (Figure 3B). The

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

• -donating or electron-withdrawing groups, work well under these conditions. However, the amine component does not react when primary or aromatic secondary amines are used. It works very well with cyclic or acyclic aliphatic secondary amines, such as piperidine or dibutylamine. In all cases, the yields are

• formation of an aminal intermediate E or the enamine derivative when they tried to obtain it from the reaction of CH2Cl2 and diethylamine in the absence of alkyne under suitable conditions (CuCl, 5 mol %, DBU 1 equiv, CH3CN, 60 °C) [62]. Only in some cases can the reaction of CH2Cl2 and certain cyclic

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

• starting materials to study the vinylogous functionalization with alkyl trifluoropyruvates. The synthesis of compounds 3 was accomplished by the reaction of cyclic ketones 1 and 5-aminopyrazoles 2 in the presence of acetic acid (Scheme 1) [30][31]. Cyclohexenones 1a–c provided the corresponding products

• 3aa–ca in good yields (47–69%). On the other hand, the reaction with tetrahydro-4H-pyran-4-one (1d) occurred with a significant decrease in yield, dropping to 11%. The yield is also affected by the number of carbon atoms of the starting cyclic ketone 1. In the case of structure 3ea, which involves 2

• -indanone, the decrease in yield is not very pronounced. However, when cyclopentanone (1f) or cycloheptanone (1g) are used, the yields dropped significantly to 5% and 6%, respectively. Next, maintaining cyclohexanone as a cyclic ketone, a series of compounds 3 were synthesized by modifying the 5

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

• ongoing challenge. Cryptophycins are a class of cyclic depsipeptides renowned for their high cytotoxicity in the picomolar range often combined with efficacy against multidrug-resistant tumour cell lines. However, cryptophycins failed as stand-alone drugs in cancer treatment, and their naturally occurring

• obtained through Grubbs metathesis and subsequent acetonide cleavage in a superior yield of 76%. The finalising steps to obtain epoxides 26 and 2 (Scheme 3) were a diol–epoxide transformation [11][19][32], including firstly the formation of a cyclic orthoester, secondly the formation of a bromohydrin

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

• spectra [1]. Moreover, the ethylene bridge creates a cyclic 8-membered core, inverting the thermodynamically stability in favor of the Z boat conformation compared to parent azobenzene, which has a stable E configuration [1][2][3][4]. Preceding studies including azobenzene-based photopharmacophores showed

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• by displacement of the mesyl group to give a six-membered cyclic carbamate, a reactivity that has been described earlier [34]. Thus, care was taken to quickly isolate compound 14 and use it immediately in the next step. Deblocking of the secondary amine by treatment with trifluoroacetic acid afforded

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

• renders them particularly suitable for the generation of arynes for subsequent use in a wide range of synthetic applications. The common approach to generate cyclic biaryl λ3-bromanes is based on thermal decomposition of hazardous diazonium salts. Herein, we disclose a mild and straightforward approach to

• diarylbromonium species by direct anodic oxidation of 2,2'-dibromo-1,1'-biphenyl. The electrochemical method provides access to a range of symmetrically and non-symmetrically substituted cyclic biaryl λ3-bromanes in moderate yields. Keywords: anodic oxidation; cyclic biaryl λ3-bromane; cyclic voltammetry

• ; electrochemistry; hypervalent bromine; Introduction Chemistry of hypervalent bromine(III) species has experienced rapid advancements during the recent years [1][2]. The remarkable nucleofugality of aryl bromides in hypervalent bromine(III) compounds has been exploited in the generation of arynes from cyclic

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

• substrate reactivity [64]. Cyclodextrins, cucurbiturils, cavitands, and calixarenes are representative [64][65][66][67][68][69][70], and typical features of these macrocycles are high symmetry and a hydrophobic cavity with polar edge groups. They tend to be synthesized as covalent cyclic oligomers in

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

• glycoside in moderate 43% yield. However, a five-membered cyclic acetal 88 as the side product was obtained which led to the determination of the plausible mechanism involving participation of the alkoxymethyl group of the C-2 position (Scheme 15). Path A in Scheme 15 designates the expected participating

• route for 1,2-trans glycoside synthesis. Path B designates the route for the formation of the cyclic ester as the side product which is only possible if the mechanism proceeds through the formation of an oxocarbenium intermediate 86. This has been effectively shown by Kulkarni and co-workers who used a

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

• stabilization of such redox states. Results and Discussion Electrochemistry Figure 2 shows the electrochemical cyclic voltammograms of 1 and 2, in which two reversible oxidation processes can be observed. By considering the half-wave potential values obtained from the cyclic voltammograms, two one-electron

• 1600–1550 cm−1 triplet. This result is fully compatible with the presence of the two rather overlapped (i.e., with similar energies) one-electron oxidations in the cyclic voltammetry of 2. The spectral resemblances for 2•+ and 22+ might also indicate that the positive charge is mainly gathered by the

• Electrochemistry Cyclic voltammetry experiments were conducted with a three-electrode geometry operating with a glassy carbon as the working electrode. A Pt-coil counter electrode. and an Ag wire, as the pseudo-reference, were used. Potential values are given with respect to the ferrocene/ferrocenium (Fc/Fc

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• coupling of alkyne 8, THIQ segment 9, and benzaldehyde would enable convergent assembly of the building blocks to produce 10 [43][44][45][46]. Removal of the cyclic acetal in 10 followed by Strecker-type conversion leading to an α-amino nitrile would enable tandem intramolecular cyclization with phenol to

• reaction involves an in situ generation of the iminium cation A followed by isomerization to the thermodynamically more stable iminium cation B. Subsequent nucleophilic attack of a copper acetylide enabled regioselective C–C bond formation at the C11 position. After removal of the cyclic acetal, the

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

• aromatic amide macrocycles [36][37][38][39][40][41][42], a class of cyclic compounds comprising a number of aromatic residues with consecutive intramolecular hydrogen bonds and amide linkages, stand out as versatile host molecules as their cavity size, peripheral side chains, and recognition sites are