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

• after deprotonation of a suitably functionalised ether at the α-carbon. Therefore, a stabilising group must be incorporated to control regioselectivity of the deprotonation as well as to increase the acidity of the α-hydrogen. Mordini et al. showed that even weakly stabilising groups such as phenyl

• react through the terminal carbon and deliver tetrahydrooxepines, especially, if the oxirane is monosubstituted (58, R1 = H). The deprotonation step can also be enabled by employing classical electron-withdrawing groups such as esters, and a particularly powerful methodology was disclosed by Bull and

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• PCET process, involving the oxidation of excited 4CzIPN* and deprotonation by a base. The resulting amidyl radical 20 smoothly abstracted a hydrogen atom from the substrate via a HAT process, generating a radical 4. This C-centered radical subsequently underwent Giese addition with activated alkenes

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

• optical absorption. The UV–vis absorption spectra, fluorescence properties and 1H NMR spectroscopy, indicate that 150 and 151 can be protonated to form the corresponding tropylium cation and consecutive dication under acidic conditions, with reversible protonation−deprotonation capabilities. Additionally

• , new OFET-based acid vapor sensors were developed from 150 by synergistically utilizing its charge transport and protonation−deprotonation properties. The solution-phase synthesis of a non-benzenoid nanoribbon from an azulene-containing polymer via alkyne benzannulation was reported by Morin and co

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• either a 1,5-hydride shift to give D or a direct cyclization with the aryl ring via intermediate E, which upon deprotonation lead to the final products 16 and 17. In a 2016 study by Van der Eycken’s group (Scheme 9), an innovative copper-catalyzed alkylarylation of activated alkenes using isocyanides as

• radical C, which adds to the N-arylacrylamide, followed by intramolecular cyclization and deprotonation to form the final products 19. To further expand the radical difunctionalization toolbox, electrochemical approaches have emerged as a green and efficient alternative, offering precise redox control

• . Based on these results and previous studies, a detailed reaction mechanism was proposed as shown in Scheme 12. The process begins with the oxidation of Cp2Fe at the anode to form Cp2Fe+, which then facilitates the deprotonation of the α-C–H bond of the 1,3-dicarbonyl compound by methoxide, generated at

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

• deprotonation, followed by chloride elimination/neutralization from the zwitterionic tetrahedral intermediate 5 to give the target molecule 1. The standard protocol for the synthesis of (hetero)aroyl-S,N-ketene acetals 8 from (hetero)aroyl chlorides 6 and 2-methylbenzothiazolium salts 7 employs a twofold excess

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• metallation deprotonation mechanisms mediated by common catalysts like Pd(OAc)2. Our methodology not only identifies potential activation sites but also addresses the limitations of existing models by including a broader range of directing groups and reaction conditions while maintaining moderate

• activation, called concerted metal deprotonation (CMD) [5][6][7]. In a concerted mechanism, the Pd atom of the catalyst forms a sigma bond to an aromatic carbon, which increases the acidity of the adjacent (alpha) proton. This allows for the simultaneous abstraction of this proton by a carboxylate ligand. A

• does not generalize well. In this study, we rely on several key assumptions that we will outline below. First, we focus exclusively on the regioselective outcomes of reactions using the concerted metallation deprotonation (CMD) mechanism between the catalyst and the substrate. It is important to note

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

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

• of the resulting acyliminium [30]. Unlike the monocyclization, which involves deprotonation of the acyliminium ion, the success of this polycyclization relies on the interception of the acyliminium ion by an aryl nucleophile, resulting in the formation of N-heterocyclic fused[6,6,5]tricycles

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

• follows a concerted metalation–deprotonation (CMD) mechanism to generate ruthenium intermediate Int-75. Subsequently, diazo compound 78 or 79 coordinates with intermediate Int-75, followed by deazidation to form the ruthenium carbenoid species Int-76. The ruthenium–aryl bond in this intermediate migrates

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

• proceeded via the anodic oxidation of diarylphosphines to diarylphosphine oxides, followed by further anodic oxidation to give phosphine oxide radicals. In the subsequent step treatment of alkoxide radicals (formed via the deprotonation of alcohols with cesium carbonate and anodic oxidation), the phosphine

• oxidation of phosphines to phosphine oxides, followed by further anodic oxidation to give a phosphine oxide radical. In the subsequent step, treatment of the thiol radical (formed via the deprotonation of thiols with cesium carbonate and anodic oxidation) with the phosphine oxide radical gave the

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

• initial deprotonation of carboxylic acid 9a by cathodically generated hydroxide is followed by anodic oxidation/decarboxylation of the formed carboxylate 9a-I to generate stabilized cation 9a-II. The latter undergoes intramolecular cyclization with the tethered N-nucleophile into cyclic aminal 6a. In a

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

• be useful for metal activation of the C–H alkyne deprotonation. The use of dihalomethanes in these reactions provides a wide scope in terms of the type of alkyne and amine that can be employed (Scheme 22) [62][63][64][65][66][67][68]. In general, aromatic and aliphatic alkynes, even with electron

• afford propargyl halide C. Finally, intermediate C reacts with the secondary amine to give the propargylamine product D. As outlined in the catalytic cycle, the presence of a base plays a dual role: co-activation of the alkynyl C–H bond through deprotonation and trapping of the HCl produced during the

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

• Br(II) followed by subsequent deprotonation to generate radical B. A following disproportionation of radical B would lead to the formation of Br(III) species C (anodic oxidation cannot be fully excluded), which undergoes intramolecular SNAr-type substitution to form cyclic λ3-bromane 1a 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

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• decrease to normal values of 1800–2000 cm−1, indicating a complete inhibition of the ESIPT process. These spectral transformations are usually caused by the formation of a strong N–H(O–H)···CN− (F−) hydrogen bond up to deprotonation [28]. Using the principle of “relay recognition” [29], we investigated the

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

• addition of Lewis base is needed. When triphenylphosphine or tri(n-butyl)phosphine were involved in the reaction, the similar SN2’ substitution of tri(n-butyl)phosphine with the elimination of carbon dioxide and tert-butoxide anion gives the phosphonium salt C. Then, the deprotonation of phosphonium salt C

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

• intermediate D via intramolecular radical cyclization. A single-electron-transfer (SET) process then occurred between the radical B and the radical D, resulting in the generation of cationic intermediate E, difluoroacetate anion and PhI. Finally, the product 3a was obtained after the deprotonation by

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

• 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

• , results in a spiro-cyclized intermediate XLI that affords the final product by deprotonation and loss of the copper species. Four-component reactions Two different four-component procedures catalyzed by Cu(OTf)2 are reported in the literature, both to access 1,2,3-triazole derivatives. The first one is a

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

• ) annulation of enals with ynamides 8 to afford axially chiral 7-arylindolines 9 was reported [20]. The reaction mechanism, rationalized by DFT calculations, is believed to occur through catalyst C3 activation of the substrate 8, dehydration, and deprotonation with tautomerization leading to the enamine

• -Breslow-type intermediates with the chiral NHC-catalyst and subsequent deprotonation toward the nitrile product. Zhang, Wang, Ye, and co-workers utilized NHC-catalysis for the atroposelective synthesis of axially chiral diaryl ethers 59 and 61 [38]. This transformation was realized via desymmetrization of

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• the squaramide moiety and a nucleophile through deprotonation as Brønsted base. On the other hand, a chiral phosphoric acid provides a confined chiral environment where the reactants are approached, activating both the azadiene by interaction with the acidic hydrogen and a dienophile bearing a

• catalysts are synthesized by joining together two fragments of cinchona alkaloids. In this manner, it is possible to obtain a symmetric catalyst, which can engage in hydrogen bonding interactions and deprotonation processes. Although they were originally used for Sharpless dihydroxylation, they have been

• patterns and aryl R2 substituents led to the desired products. However, the presence of a cyclopropyl or isopropyl R2 substituent, led to a complex mixture of products (Scheme 15). In the mechanism proposed by the authors, (DHQ)2PHAL XIII provokes the deprotonation of the γ-nitro ketone at the α-position

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• deprotonation would complete the pathway. The alternative mechanistic proposal is an SN2 reaction [40][41][42] between 1a and the iodonium ion 2a’, which directly furnishes B without invoking halogen bonded adducts. To assess which of these mechanistic possibilities was more probable, we turned to computational

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• 32.2 [4], respectively (Scheme 1) [5][6]. The reaction enthalpy for deprotonation of CpH is ca 20 kcal/mol less endothermic than DPMH and ca. 24–27 kcal/mol less endothermic than 1,4-pentadiene (PDH; pKa ≈ 35 in DMSO) [3], values strikingly similar to the resonance stabilization energy estimated for

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

• [48]. Therefore, most of the work involving metal-free porphyrins is limited to investigations on N–H tautomerization and protonation–deprotonation studies [49][50][51][52]. However, there are several chemical tools to convert the planar geometry of porphyrins to nonplanar, such as functionalization

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

• -AcrClO4 as the photocatalyst has been disclosed (Scheme 24) [67]. According to the authors, the irradiation of the photocatalyst (Acr+-Mes) A with a blue LED leads to the excited state (Acr·-Mes·+) B. The aliphatic carboxylic acid 66 is converted by deprotonation to the corresponding carboxylate, which is

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• our laboratory, we have explored the synthesis of 3,3,3-trifluoro- and 2,3,3,3-tetrafluoro-N-substituted propanamides, contributing to the field of fluorinated amides [25]. We have also investigated deprotonation at the α position of other fluorinated carbonyl derivatives as a route to new building