Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• reactivities of the two diastereomers. Although these findings strongly support the occurrence of a partial kinetic resolution, further kinetic measurements would be required for definitive confirmation. A plausible mechanism is outlined as follows. First, the sulfenamide 1 is oxidatively brominated by N

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• . Although the activation mechanism was not proved unambiguously, it is assumed that steric effects of the chiral fragment together with a network of noncovalent interactions, including halogen and hydrogen bonds, are responsible for the high enantioselectivity of the reaction. Further developments of the

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• theory (DFT) methods. The dyes also exhibit chemosensor properties, showing selectivity for cyanide via a Michael addition mechanism that causes the disappearance of the ICT band, and a significant color change was observed in both organic and aqueous media. In addition, the interaction mechanism between

• under ambient light. In addition, interaction mechanisms of dyes with cyanide were studied using the 1H NMR titration method, and it was determined that they interacted through an addition mechanism. Photophysical properties and interaction mechanisms of the compounds were also supported through density

• groups is disrupted. These results strongly suggest the addition of cyanide to the vinyl bridge. Furthermore, the color of dyes 2a–c, blue, green, and pink, respectively, under ambient light changed to yellow when interacting with cyanide. The interaction mechanism was determined by 1H NMR, and the

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• –C2H protons of the cyclopropane ring (3JH(1)H(2) = 5.7–7.5 Hz) indicate their transoid arrangement [38][39][45]. This makes it possible to assign 1SR,2RS configurations to the stereocenters. The proposed mechanism for this transformation is depicted in Scheme 6. Michael addition of the CH-acid anion I

• -fused trichloromethylnitrocyclopropane 6. Synthesis of spiro-fused trichloromethylnitrocyclopropanes 7–9. i: 1.5 AcOK, MeOH, rt, 3 h. Main NOE correlations in 9a, 9b. Proposed mechanism of the formation of trichloromethylnitrocyclopropanes. Reaction of compound 1 with malononitrile leading to

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• intramolecular addition to the olefin, affording the cyclized acetal product 4. The reaction proceeded efficiently across a range of substrates bearing various substituents at R¹–R⁴, delivering the desired cyclized products 4a–f in good yields. The proposed mechanism is illustrated in Scheme 1C. Initially

• , demonstrating excellent functional group tolerance. The proposed mechanism is shown in Scheme 2C. Zirconocene dichloride is first reduced by zinc dust to generate ZrII. The resulting low-valent zirconium species reacts with the alkyl iodide to form a metal-centered radical intermediate. This species undergoes

• molecules such as allose (23i) and cholesterol (23k), delivering the desired alcohols in good yields with excellent regioselectivity. The proposed mechanism is shown in Scheme 5C. Homolytic cleavage of the C–O bond in the epoxide generates a strong Zr–O bond, while the resulting alkyl radical abstracts a

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• chlorine is associated with an increase in energy of the lowest unoccupied molecular orbital of halogen molecules and a decrease in their electrophilicity. Therefore, if an electrophilic mechanism takes place, iodine apparently reacts with the main conformer faster than a transition to conformer 2' may

• possibility of i-halogenation via a chain radical mechanism (Scheme 3). The initiation stage includes an oxidation of anion 2 into the corresponding radical 13 which in turn reacts with halogens to form products 4a,b and a halogen atom which can also oxidize the anion. Quantum chemical calculations revealed

• negative free energy changes for all the stages of this reaction. A chlorination experiment with 2,2,6,6-tetramethylpiperidinyloxyl revealed a trace amount of a trap product detected by high-resolution mass spectrometry to support the radical mechanism. However, this does not exclude the possibility of a

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• synthesis lies beyond the scope of the present discussion. Regarding the use of color in graphical representations, structural highlighting was applied selectively, only when judged necessary in the clear identification of the transformation or mechanism depicted. Chapter 2 highlights key applications of

• unable to efficiently separate 61 from side product 94, which was likely formed via addition of acetyl chloride to 61 followed by conversion of the ketone to the alkenyl chloride. Regarding the mechanism (Scheme 18B), acid-catalyzed enolization of the ketone is proposed (enol I), followed by acetylation

• compound loss or degradation at the purification step. 1.2 Exchange reactions This chapter deals with exchange reactions, meaning that a given substituent on the alkene is formally exchanged for chlorine. The reactions are very different from each other in terms of mechanism and for a full discussion the

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• nucleophilic substitution of –ONO2 groups. To clarify the reaction mechanism, cyclic voltammetry (CV) studies were conducted. CV curves of cyclohexanone oxime (S1), 1-bromo-1-nitrosocyclohexane (S2), 1-chloro-1-nitrosocyclohexane (S3), 1-nitrosocyclohexyl acetate (S4), 1-nitro-1-nitrosocyclohexane (1c), 1

• product nitro-NNO-azoxy propane 2a exhibits an oxidation peak at +1.68 V (Figure 2, pink curve). Despite the lower oxidation potential of 2a, we speculate that an excess of ADN suppresses competitive oxidation of the reaction product. To gain insight into the reaction mechanism, control experiments were

• studied reaction was also carried out under controlled potential conditions (Scheme 4, reaction 2) at E ≈ 1.8 V for 2.0 F per mol 1a. In this case, the formation of 2a was observed in a 68% yield. To gain insight into the reaction mechanism of the discovered nitro-NNO-azoxylation process quantum chemical

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• minor when heated in 1,4-dioxane (Scheme 3, Table 3). Previously, we proposed and experimentally confirmed an aldol mechanism underlying the three-component cyclization of polyfluoroalkyl-3-oxo esters with α-methylene ketones and amines in piperidone derivatives. According to this mechanism, the key

• , AcOH, Et3N, 60 °C. The proposed mechanism of three-component cyclization of 3-oxo ester 1, methyl ketones 2a–d and 1,3-diaminopropan-2-ol (3). Optimization of the reaction conditions for ethyl trifluoroacetoacetate (1), acetone (2a) and 1,3-diaminopropan-2-ol (3). The conversion and the preparative

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• Jai Parkash Sangeeta Saini Vaishali Saini Omkar Bains Raj Kamal Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119, India School of Basic and Applied Sciences, Raffles University, Neemrana, Rajasthan 301705, India 10.3762/bjoc.21.208 Abstract In this paper, the mechanism

• nature of para-substituents on the reaction mechanism. The substituents considered in the study include -OCH3, -SCH3, -Cl and -NO2 groups. For these chalcones, different possible pathways at various steps during the reaction are investigated leading to formation of α,β-ditosyloxy ketones and β,β

• -ditosyloxy ketones. It is found that the mechanism for the formation of α,β-ditosyloxy ketone involves only electrophilic addition of HTIB, and the mechanism is the same for all studied chalcones, irrespective of whether an electron-donating or electron-withdrawing substituent is present on the aryl ring

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• (c, d) reaction mixtures in MeCN. Examples of hydrothiocyanation/cyclization of alkynes. Plausible reaction mechanism. Oxidation of isothiazolium thiocyanate 2a. Screening of reaction conditions. Scope of iminopropargyl alcohols 1. Supporting Information Supporting Information File 10: Full

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• compounds 3n and 4n was carried out using torsion angle analysis and 13C NMR chemical shift calculations to evaluate the absence of expected signals in the NMR spectra of these compounds. Their photophysical properties were also assessed, confirming a preference for a fluorescence mechanism via an ICT

• . Photophysical studies indicated a fluorescence mechanism via intramolecular charge transfer (ICT). Results and Discussion Synthesis of 5-arylidene derivatives under microwave heating To find the ideal reaction conditions for the synthesis of 5-arylidene derivatives, benzaldehyde (1a) and rhodanine (2a) were

• decrease in yields (Table 1, entries 19–21). To confirm the critical role of ethylenediamine in the reaction mechanism, an experiment without its presence was conducted, resulting in only 2% of the desired product (Table 1, entry 22). With the optimized reaction conditions established, this methodology was

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• Lewis acid-mediated traditional Friedel–Crafts acylation of 2-methoxynaphthalene typically proceeds at the ortho positions relative to the methoxy group due to the electron-rich nature of these sites, while the meta position remains deactivated under the ionic mechanism. Notably, the present work

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• . While its mechanism remains incompletely understood, this additive’s unique efficacy in such transformations is unprecedented. Subsequent steps involved hydroxylation of the double bond and the protection of the vicinal diol as a dimethyl ketal giving ester 100. Oxidative dehydrogenation, benzyl

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• measurably bioactive, including those serving as controls for the five bioactive derivatives, highlighting the additional importance of structural rigidity on bioactivity within this series. Elucidation of the mechanism of action for these bioactive pentacyclic compounds will be the focus of future

• similarity showed significant antimicrobial potency towards Gram-positive bacteria and yeast relative to their non-annulated control analogs as well as to the other annulated pentacycles in this study, warranting a future investigation into their possible mechanism of action. Studies focusing on the

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• bilayers through the shuttling of the macrocycle carrying the ions or through a relay mechanism [10][11]. In one example, the isomerization of an azobenzene photoswitch incorporated into the axle was used to modulate the shuttling rate of the macrocycle and, consequently, the efficiency of potassium ion

• mechanism of membrane perturbation. Notably, the effect did not appear until after the fourth irradiation cycle. It required multiple light irradiation cycles to trigger a sudden spike in dye release, in contrast to the gradual increase observed with rotaxane 1 from the first cycle onward (Figure 5). Since

• be attributed to the same light-induced phenomenon observed in EYPC/Chol 8:2, which suggests a different mechanism than the disruption caused by azobenzene photoisomerization in rotaxane 1 (Figure 4b and Table 1). Interestingly, membrane rigidity also appears to decrease the effect caused by the

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• thiophene, promoting further study of these structures and reaction mechanism. 1H NMR spectroscopy of the obtained mixture provided the first key information about its nature, namely the presence of two major products 2 and 3, both of which showed three characteristic singlets with signal integration 1:3:3

• , necessitates consideration of a reaction mechanism beyond straightforward nucleophilic substitution of the nitro group in ester 1. Although the initial reaction probably involves a nucleophilic attack by the S-nucleophile on the activated thiophene ring, resulting in displacement of the nitro group, the

• subsequent fate of the intermediate appears to be critical. Based on our observations and literature data, a probable reaction mechanism was proposed. The initial nucleophilic substitution of the nitro group in ester 1 by the AcS− anion yields the S-acetyl derivative (intermediate A) and NO2− anion. The key

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• palladacycle 6 as the catalyst, and the desired nitrated product 2a was obtained in 48% yield (Scheme 5c). This result supports the involvement of palladacycle intermediate 6 in the catalytic cycle. Proposed mechanism Based on our experimental results and related literature precedents [68][69][74][75][76][77

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• furanose form through steric and electrostatic effects. In our previous work [24], we investigated the energetic aspects of the pyranoside-into-furanoside (PIF) rearrangement that proceeded under acid-promoted sulfation and whose mechanism was studied by us previously [25] along with the mechanism of

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• formation proceeded through an SN2-type nucleophilic substitution mechanism (Scheme 1). In 2025, Li and co-workers reported a highly efficient rhodium-catalyzed enantioselective C–H selenylation reaction of 1-arylisoquinolines with diselenides, employing 3,5-(CF3)2C6H3CO₂Ag and AgSbF6 as additives [19

• reaction yielded the desired product at room temperature with high regioselectivity and stereoselectivity (E/Z ratio >99:1). Notably, when chiral catalyst (cat.1) was used, the reaction afforded the axially chiral product 9 in 43% yield with 84% ee. The proposed mechanism proceeds as follows. Catalyst cat

• alkyne insertion step may be rate-limiting, as it involves the participation of selenol, alkyne, and the rhodium catalyst. The Rh(III) mechanism appears to be more plausible than route B, which can be attributed to the enhanced ion-pairing effect resulting from the higher oxidation state of rhodium

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• via the oxo-nitrile mechanism, with formation of the corresponding Α-pentacyclic 3-ethyl α,β-alkenenitriles 49 and 50 with yields of 44% to 45% (Scheme 9). Cytotoxic screening was performed using the MTT assay with a panel of 7 human tumor cell lines, and showed that the synthesized triterpenoids 47

• aldehyde 53 [39] (Scheme 10). The key steps in this synthesis are based on an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction [40], followed by a unique benzilic acid-type rearrangement under very mild conditions [41]. A step-by-step mechanism for the benzilic acid-type rearrangement of

• reported a stereospecific reduction of an acyloin ring controlled by the chirality of a glucose fragment at position C5, and suggested a possible mechanism for hydrogen migration during the conversion of C5 (sp2) to C5 (sp3). The key 3,4,6-trihydroxycyclohexadienone 76 was obtained by a sequence of Friedel

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• the cycloaddition reaction in a non-polar solvent, such as methyl laurate, indicates that it proceeds via a non-polar mechanism. The lower polarity of the activated complex in comparison to the starting compounds supports the higher reaction rate in an non-polar solvent such as methyl laurate [61][106

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• . Third, the introduction of an ortho-methyl substituent on the ketone moiety (3m) likewise suppressed product formation, likely due to steric hindrance interfering with cyclization at the C3 position of the indole ring. Based on literature precedents [15][16], we propose a mechanism involving a radical

• mmol scale experiment. The scope of the Fe-catalyzed spirocyclization. aIsolated yield of the 4.2 mmol scale experiment. The proposed mechanism of product 4 formation. Supporting Information Supporting Information File 2: General reaction procedures, compound characterization data, and copies of NMR

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• work represents one of the earliest comparative studies on the anion-binding behaviors of carbazole-based structural analogs, demonstrating that a flexible macrocycle markedly improves iodide binding affinity via an induced-fit mechanism. The flexible analog PBG exhibits a 22.78-fold higher

• demonstrated that flexible PBG achieves superior I− binding (KPBG = 1.387 × 105 M−1) through induced-fit conformational adjustments, whereas rigid WDG (KWDG = 6.089 × 103 M−1) is constrained by preorganized cavity geometry, adhering to a conformational selection mechanism. This work elucidates the synergistic

• spectroscopy and fluorescence spectroscopy, combined with Benesi–Hildebrand equation [23] and nonlinear curve fitting [24]. The purpose of systematically exploring the difference between the two types of recognition of I− is to reveal the regulation law of conformational dynamics on the binding mechanism

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

• CC BY 4.0. (a) Structure of the [2]rotaxane and (b) mechanism for K+ cations transport across lipid bilayers. Figure 6 was adapted from [51], C. Wang et al., “A Light-Operated Molecular Cable Car for Gated Ion Transport”, Angew. Chem., with permission from John Wiley and Sons. Copyright © 2021 Wiley