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

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• cleavage proceeds either by activation of a nucleophile that attacks C1' or by stabilization of the leaving group, which could either be the nucleobase or an oxocarbenium ion [31][36]. As such, the oxocarbenium ion is a species formed during the glycosidic bond cleavage, which may be present as an

• intermediate or a transition state depending upon the accumulation of the positive charge on the sugar ring (Figure 2). As a result, any change in the nucleobase–sugar connectivity (C–N) affects the formation of the oxocarbenium ion and thus influences the stability (or instability) of the nucleoside analogues

• ) results in an oxocarbenium ion [62][70][80][81][82][83]. Reduction of this intermediate by various silanes gives C-nucleosides resembling the canonical nucleosides [82][83]. The stereochemical fate of oxocarbenium ion reduction is dictated by the conformation and stability of the oxocarbenium ion, which

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• recovered through column chromatography. Therefore, we conclude that the reaction would have followed an intermolecular glycosylation reaction through an oxocarbenium ion. Combining all of these observations and results from earlier literature reports, a plausible reaction mechanism for the electron

• the glycosyl donor by increasing the acidity of ammonium salt X to form an oxocarbenium intermediate B. Further, the nucleophilic attack of the acceptor to the oxocarbenium ion B would produce the desired glycoside 5. Higher α-selectivity may be attributed to the anomeric effect. Conclusion In

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• evolve into several reactive species, such as oxocarbenium ion 79, α-triflate 80, disulfonium ion 81, and dioxalenium ion 82. The nucleophilic attack of the intermediate by a thioglycosyl acceptor would generate the desired glycoside 78. Pioneered by Crich and co-workers, low temperature NMR studies have

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• retention of configuration (Figure 5) as first described by Koshland [53]. However, in the case of GHs, the mechanism generally implies the intervention of two amino acid side chains, typically glutamate or aspartate, and goes through oxocarbenium ion-like transition states. Inverting GHs operate via a

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• THF hence forming an oxocarbenium ion. The latter is subsequent attacked by the nucleophilic alcohol to provide the 1,2-trans glycoside with good diastereoselectivity and moderate yield. This methodology holds tremendous potential if the alcohol acceptor is a saccharide moiety as the

• very common and well-studied. Typical Lewis acids employed for anomeric activation are TMSOTf and BF3·Et2O (Scheme 14). The reactions proceed through an oxocarbenium ion that was very recently observed by NMR under cryogenic (−40 °C) conditions stabilized by the HF/SbF5 superacid [52]. The highly

• electrophilic carbon adjacent to the oxocarbenium ion then reacts with the nucleophilic acceptor in either and SN1 or SN2-like mechanism depending on the chemical stability of the glycosyl cation [53]. The stereochemical outcome of the reaction is generally dictated either by neighboring-group participation of

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -2-ylamides 54 in good yields (Scheme 16a). The mechanism for this cyclization as proposed by the authors is depicted in Scheme 16b [98]. Following this work, the Čikotienė group studied the metal-free halogen, chalcogen, or oxocarbenium ion-mediated cyclization of a series of N-propargylthioureas 55

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• 2-phthalimido, N-Troc or N-Ac group. It was suggested that the bulky DTBS group is shielding the β-face and thereby preventing attack from that face of the oxocarbenium ion. This methodology has been applied to the synthesis of glycolipids and was shown to also work with 2-O-benzyl [56] or 2-O-TBS

• was proposed that the selectivity was caused by a favored β-attack on the oxocarbenium ion in an E3 conformation as the corresponding α-attack would lead to an unfavorable eclipsed conformation. The exchange of the 2-O-benzyl with a 2-O-TIPS leads to some erosion of stereoselectivity though the donor

• conformational change is not needed to expel the sulfonium ion. This is not the case with the β-anomer. Selectivity is mainly controlled by sterics and hence the α-glycoside is kinetic product as the alcohol approach the oxocarbenium ion intermediate from the exo-side. Glycosylation with sulfoxide 1