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

• ring contraction reaction on simple cyclohexanones to synthesize functionalized di- and triquinanes [51]. Treatment of 6-oxabicyclo[3.2.1]octan-8-one 86 with BF3·Et2O (2 equiv) promoted the activation of the carbonyl group in 87 by the Lewis acid, leading to the formation of an oxocarbenium ion 88

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• sofosbuvir (2). Fluorination at C2 in the nucleoside results in metabolic stability and resistance to hydrolysis as it destabilizes the formation of a C1 oxocarbenium ion [5][6]. Trifluoromethylated γ-butyrolactones also find applications as antiviral agents, for example, lactone 4 which has activity against

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• substituents, thereby minimizing the likelihood of oxocarbenium ion formation from the silyl aldoside acceptors 50 and 53 (Scheme 5). Nucleophilic attack by 1-O-trimethylsilyl β-pyranosides 50 or 53 on the α-face of the oxocarbenium ions afforded the corresponding β-ketopranosyl α-aldopyranosides 51 and 54

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

• in which fluorine can control the rotation of the C-5–C-6 bond is seen when a C-6-fluorinated sugar is converted into an oxocarbenium ion (e.g., 73, Figure 10). The C-6–F bond of 73 preferentially orients over the sugar ring, due to a combination of electrostatic attraction between the partially

• negative fluorine atom and the positively charged C=O+ moiety, and σC–H → σ*C–F hyperconjugation. The fluorine atom thus shields the top face of the oxocarbenium ion, and this has flow-on effects on the rate and stereoselectivity of subsequent glycosylation reactions [139]. Another important rotatable bond

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

• directions away from the central oxocarbenium ion intermediate in the limiting dissociative process involving diastereomeric ion pairs. Destabilisation and greater reactivity of the oxocarbenium intermediate causes the nucleophilic acceptor moiety to attack in a concerted process following a classical SN2

• as the participating group facilitating the formation of a 1,2-trans glycoside (Scheme 2). In general, the cleavage of the activated anomeric leaving group of the glycosyl donor 9 leads to the formation of an electron-deficient oxocarbenium ion 10. The participating vicinal acyl group interacts with

• by the participation of the phosphate group by reverse anomeric effect. However, according to the authors, the phosphate groups acting as a neighbouring participating group forming the corresponding oxocarbenium ion intermediate 73 (path B, Scheme 13) seemed to be more plausible. Non-ester

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

• . Photocatalytic oxidation of radical A with [IrIV(ppy)3] regenerates [IrIII(ppy)3] and completes the photoredox catalytic cycle. The Bronsted acid catalyzes the formation of the isochroman oxocarbenium ion B, which is then nucleophilically attacked by TBHP to produce the target peroxide 69. Heteroatom (N, O

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• requires 18 hours (Scheme 16). A proposed catalytic cycle is shown in Scheme 17. In this reaction, the aromatic acetal 80 gives rise to a hydrogen-bonded triflate 82 and oxocarbenium ion 81. The latter quickly reacts with BocNH2 forming the ArCH=HN+-Boc iminium–triflate ion pair 83. Notably, the attack of

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• skeletal rearrangement (vide infra). Inclusion of the soft-nucleophile allyltrimethylsilane in the reaction of 10b to trap potential oxocarbenium ion intermediates also resulted in a complex mixture. During the isolation of the chloroalkyl ether products 11a–f, it was apparent that hydrolysis occurred

• chlorosulfite 25 or the alkoxytriphenylphosphonium chloride 26, respectively. With heating, SO2 or triphenylphosphine oxide is extruded with a concerted migration of the neighbouring O8 leading to an oxocarbenium ion 27, which is then trapped with chloride giving the observed products. The crystal structure for

• bond migration. This is a mechanistic difference to the related 1,2-oxygen migration reactions of spiroacetals that involve alkoxy intermediates reported by Suarez and co-workers [33][34]. The presence of oxocarbenium ion 27 is inferred due to the formation of two diastereomers in Karban’s previous

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• and stereoselectivity (Scheme 8) [58]. The mechanism of this reaction differs from the previously reported ones and proceeds through the in situ generation of nucleophilic and electrophilic partners which provides new opportunities for enantioselective oxocarbenium ion-driven CDC processes. Due to an

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• oxocarbenium ion 16. Subsequent loss of the ethyl group (either as ethyl formate upon solvolysis with the formic acid co-solvent or as ethanol upon aqueous workup) gives lactone 9, which features a strained trans-fused 6/5 ring system. Although this lactone survives aqueous workup at neutral pH, it is rapidly

• to give oxocarbenium ion 17. In comparing conformers 12b and 12c, it appears that the chair-like transition state 12c should be lower in energy since the more sterically demanding cyclohexenyl ring is located in a pseudo-equatorial position. Although we did observe a slightly higher yield of 10 as

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• cellulose and chitin and approximation to the structure of lignin. Tensile forces by ball milling change the conformation of a chitin model compound. This deformation facilitates the subsequent cleavage of glycosidic bonds to produce oxocarbenium ion intermediates for hydrolysis [45]. (a) Representation of

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• ). The enol acetate A first undergoes anodic oxidation to form a radical cation intermediate B, which is then intercepted by azidotrimethylsilane to afford the benzyl radical C. Subsequently, this radical is further anodically oxidized to its oxocarbenium ion intermediate D, which finally reacts with

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -promoted condensation of a homoallylic alcohol and an aldehyde to give an oxocarbenium ion, which is then reacted with an olefinic/alkynic bond generating a carbocation that undergoes a Friedel–Crafts reaction. Given the potential value of tetralin-2-ol scaffolds to drug research programs, we decided to

• develop a novel Prins/Friedel–Crafts cyclization strategy for the synthesis of 4-aryl-2-hydroxytetralins starting from 2-(2-vinylphenyl)acetaldehydes (Scheme 2). In this protocol, we envisioned that the aldehyde 5 would give rise to an oxocarbenium ion species 6 upon treatment with a Lewis acid. The

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• for the synthesis of O- [4][34][35] and C-glycosides [36] and by employing more reactive armed [1] glycosyl fluorides. In glycosylation reactions the solvent plays a critical role in terms of stabilizing the oxocarbenium ion intermediate and/or affecting the α,β-selectivity [1]. In 2017, Matheu et al

• stabilize the oxocarbenium ion formed from glycosyl perchlorate that is generated in situ from glycosyl chloride and AgClO4 [56]. Apart from that, SO2 has considerable affinity to the Lewis basic halide ions [57][58][59]. Kuhn et al. [60] and later Eisfield and Regitz [61] have published ab initio studies

• halosulfites may dissociate. Thus, we proposed that a plausible formation of the fluorosulfite species and stabilization of the oxocarbenium ion intermediate could facilitate the glycosylation with glycosyl fluorides as glycosyl donors in liquid SO2 without the need of external promoter. Results and Discussion

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• of aldehydes or ketones in the presence of acid (Scheme 2) [25]. Although the Kriewitz reaction was an ene reaction, the mechanism of the reaction was described to proceed via an oxocarbenium ion intermediate captured by a π-nucleophile, followed by the addition of an external nucleophile, leading to

• to give oxocarbenium ion 15, wherefrom two competing transition states, 15a and 15b, can possibly form. In the 6-membered chair-like transition state 15a, there is a 1,3-diaxial interaction between “H” and the substituent R2, while for the other five-membered transition state 15b, there is no such

• an oxocarbenium ion is generated from a masked aldehyde bearing a homoallylic alcohol moiety has been examined. In this context, the α-acetoxy ethers with different functionalities at C4 were examined in the presence of a variety of Lewis acids, and it was found that the α-acetoxy ether (R)-42

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• modified with 4'-fluoro modifications have more labile glycosidic linkages under similar conditions [203][204]. Rosenberg attributed this contrast to the electronegativity differences between the groups and the effect this would have on the stabilization of the resulting oxocarbenium ion [202]. Oligomers

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• derivatives readily underwent intramolecular Friedel–Crafts-type C–C bond formation followed by dehydration or alcohol elimination, leading to the construction of benzene rings in the biaryl systems (Scheme 2) [20][21]. The reaction proceeded via oxocarbenium ion intermediates stabilized by HFIP. This method

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• oxocarbenium ion is substituted, two diastereomeric half-chair conformers are possible: 3H4 and 4H3 (shown for a 4-substituted pyranose cation in Scheme 5). Both may undergo attack by a nucleophile in two ways: on the axial trajectory from the top or the bottom face. Such an event would result in the formation

• conformer. Therefore, once the ground conformer of the oxocarbenium ion is established, this logic may be used to predict the reaction’s stereochemistry. The same principle may be successfully applied to reactions of iminium cations. We have previously shown that in the case of glucose- and galactose

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• the secondary 3’-hydroxy functions. Steric effects on the hydrolysis rate are supposed not to be important, because the rate-controlling step of the hydrolysis is suggested to be the unimolecular degradation of the protonated substrate. This releases the stabilized oxocarbenium ion as an intermediate

• slightly more acidic than the 5’-hydroxy group, but absolute values for the acidity constants could not be reliably determined. The hydrolysis of the acetals is suggested to follow most often the A-1 mechanism via formation of an oxocarbenium ion [11]. Polarity effects and the stability of the formed

• oxocarbenium ion determine, which one of the alkoxy groups is protonated and released as an alcohol. The two proposed competing pathways are illustrated in Scheme 2. Salomaa has shown earlier [12] with formaldehyde acetals that the structural effects on the stability of the oxocarbenium intermediate are

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• (Scheme 6 vs Scheme 7). The catalyst abstracts and binds the chloride anion and forms an ion pair [cat•Cl]− and oxocarbenium ion [18]+. Silyl ketene acetal 11 reacts with this ion pair complex to product 19 [77][78]. Only with DCM as solvent, product 19 of the reaction has been isolated (Table 10

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• aldehyde- and ketone-based intermediates, respectively. Keywords: carboxonium ion; glycosylium ion; oxacarbenium ion; oxocarbenium ion; oxycarbenium ion; Introduction There is much confusion in the literature over the name of the intermediates R1C(=O+R3)R2 (R1, R2, R3 = H or organyl [1], 1; Figure 1). In

• parent structure was meant (note the use of carbenium and not carbonium ion), then an oxidanylium ion (4) would result (Figure 2). Either way, this term is not appropriate to describe intermediate 1. Oxocarbenium ions Secondly, the term “oxocarbenium ion” presents additional confusion because this term

• is also used to describe other intermediates. For example, the prefix “oxo” denotes the characteristic group “=O” [26][27] and, consequently, “oxocarbenium ion” is a carbenium ion with the group “=O” (i.e., a synonym of an acylium cation, 5; Figure 2), which is the other use found in the literature

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• can be explained as follows. In the first step, the 1,2-isopropylidene group is cleaved by the Lewis acid and an oxocarbenium ion (9, Scheme 2) is generated [30][32]. With electron-withdrawing groups like acetyl, benzoyl or pivaloyl the carbohydrate gets more electron deficient and the generation of 9

• and 93:7 β:α, respectively (Table 1, entries 1 and 2) to a β:α ratio of 66:34 (Table 1, entry 9). These ratios can be explained by the mechanism of the Ritter reaction. The oxocarbenium ion 9 exists as an equilibrium of two conformer half-chair forms 9a and 9b (Scheme 5). Theoretical investigations of

• carbohydrate chemistry a well-known phenomenon is participation of neighboring groups. An oxocarbenium ion is often stabilized by protective groups. Esters are a class of protective groups which often participate in such a manner [43][44]. 7j–m bear at least one ester protective group. We propose that when R1

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• anomerically modified carbohydrate with inversion of configuration at the anomeric center, according to a SN2 mechanism. Pathway A can also proceed through a SN1 mechanism when the intermediate glycosyloxyphosphonium ion is less stable. Then, it can decompose into the corresponding anomeric oxocarbenium ion

• and phosphine oxide. The oxocarbenium ion would then react with the NuO− anion in a SN1 mechanism. While this would lead to racemization under normal circumstances, in most carbohydrates, participation effects of neighboring groups in the vicinity (typically at the 2-position of the sugar ring) affect

• this case, the absence of a neighboring group in position 3 of the sugar ring could account for low stereoselectivity. To explain the lack of stereoselectivity, the authors considered a SN1 reaction mechanism, involving the respective oxocarbenium ion or, alternatively, the formation of both α- and β

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• oxocarbenium ion 101 to serve as an intermediate, giving a nucleoside 102. First, we attempted model reactions of the oxidative coupling to enol ether using a TMSOTf/PhI(OAc)2 system. After several attempts, we found that the reaction of 3,4-dihydro-2H-pyran (DHP, 103) with PhI(OAc)2 and TMSOTf, starting at

•  7. The reaction of iodosylbenzene and electrophiles, e.g., triflic anhydride or Lewis acids, should generate a potent thiophile 143 that reacts with thioglycoside 144 to form an oxocarbenium ion 145. The resulting oxocarbenium ion 145 should in turn react with a sugar acceptor to give the