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

• halogens, nitriles, alkenes and heteroaryls. On the other hand, this methodology suffers from relatively low diastereoselectivity as the dr lies between 1:1 and 2:1. DFT calculations suggested the reaction proceeds through nitrogen elimination, oxonium ylide 119 formation, homolytic cleavage and radical

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• intermediate 7, the carbonyl oxygen interacts with AlCl₃, enhancing the electrophilicity and promoting the rearrangement to form stable oxonium ions. The removal of water from 7 is facilitated by protonation, producing reactive carbocations which undergo dehydrative aromatization to produce products 8

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

• cinnamate (44) via an electrochemical method using TBAF as the supporting electrolyte (Scheme 56) [99]. Under these conditions, the aldehyde was oxidized to give an oxonium cation intermediate 176. Moreover, Babu and co-workers (2024) oxidized an imine, cinnamalaldehyde N-tosylhydrazone (177), by using TBHP

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

• -benzylcarbamoyl (BnCar) group was not responsible for any formation of any oxonium ion in the intermediate steps. Instead, the BnCar group in the C-2 position stabilised the α-triflate (Scheme 11) as proposed by the Deslongchamps model [135][136] which further initiated the formation of 1,2-trans or β-glycosides

• 9-anthracenylmethyl group in the C-2 position which rendered neighbouring group participation effectively via a favourable π–π interaction between the p-orbitals of the stabilised oxonium ion intermediate and the aromatic ring of the protecting group to yield 1,2-trans selective products. Increasing

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• enough to displace the iodane to form the oxonium species A. When the carboxylic acid is used, the oxygen in the lactone intermediate is less reactive and so substitution of the iodane by fluoride is more favourable and the branched product is formed. In addition to aminofluorination, Szabó also reported

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• molecule on this cation, followed by tautomerism (path a). The intramolecular attack of an amide carbonyl on this cationic site in intermediate 10, leading to the formation of oxonium ion 11, is also possible (path b). After the addition of water, the formed hemiacetal 12 was hydrolyzed to give the

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• charged pyridinium or imidazolium residues (Figure 7D) [88]. The presence of a stable positively charged moiety in the linker has, in case of imidazolium, increased by 70–90% the relative abundance of modified peptides. In combination with release of the glycan-related oxonium ions during fragmentation

• yields after HCD fragmentation a set of diagnostic ions including the prominent oxonium-biotin and dehydrobiotin ions (Figure 8B). Importantly, the oxonium-biotin fragment was found in more than 99% of the assigned spectra, so-called peptide spectrum matches (PSMs). The second most frequent diagnostic

• presence of the PEG moiety, which has likely only minimal influence on the diagnostic peaks’ generation. Taken together, consideration of the oxonium-biotin and dehydrobiotin diagnostic ions increases the confidence in the identified probe–peptide conjugates. Next, selective elution of the probe–peptide

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• radical cation 81 and Mes–Acr because of the favorable π–π stacking. Ethyl vinyl ether, which is the most nucleophilic molecule in the reaction, combined with radical cation 81 to form the oxonium radical 82, which could proceed in two directions: 1) β-elimination, yielding radical 83 and 2) photoinduced

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

• oxidant to generate an oxygen-radical cationic intermediate, which undergoes abstraction of a hydrogen radical (or loses a proton first, followed by an electron) to afford an oxonium ion intermediate. Finally, the oxonium ion is attacked by various nucleophiles to obtain the target functionalized product

• extract a hydrogen from the ether C (sp3)–H bond to form radicals. Subsequently, a single electron transfer (SET) leads to the oxonium species. Then, the enamine generated in situ from methyl aryl ketone and pyrrolidine undergoes a nucleophilic reaction with the oxonium species followed by hydrolysis to

• metal-triggered oxidation of the ether substrate to obtain the corresponding radical or oxonium ion as the key intermediate to obtain the final coupling product. Subsequently, some novel Co-catalyzed coupling mechanisms have been proposed. In 2016, Lu et al. reported that the Co/TBHP catalyst oxidation

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• with NaHSO4 in a mixture of methylene chloride/MeOH proceeded as described in Scheme 5. First, the C=O group of the ester prefers to attack the protonated epoxide to give intermediate 15. Then, water, which is available in methanol as an impurity, attacks the oxonium ion to give dealkylation product 10

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• . C–O cleavage, Figure 1A) through H-atom abstraction from a photoexcited intermediate, which produces an oxonium-type intermediate (in brackets). Hydrolysis of this intermediate then affords an alcohol product. Recently [16][17], we demonstrated that vinylogous analogues of this mechanism (Figure 1B

• nitroso 3, and related compounds 4 and 5 are all consistent with the classical C–X cleavage mechanism and with hydrolysis of the presumed oxonium intermediate 6’, but are inconsistent with the production of formyl products. In contrast, photoirradiation of the same alkenyl ether 6 under acidic conditions

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• the furan framework. Following Fe-catalyzed oxidation, the resulting oxonium cation can be deprotonated to afford the final dihydrofuran. Further, this inter-/intramolecular radical addition/cyclization methodology has been applied for the synthesis of various substituted dihydropyrans [100][101] and

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• -based lactol. This is a necessary requirement to produce the desired stereochemistry in the product. It was extensively reported that the β-selectivity could be due to the formation of an oxonium ion, which is stabilized through anchimeric assistance of the ʟ-menthyl ester function. The method requires

• stereoselectivity during β-selective glycosidic bond formation. The general pathway for glycosidic bond formation (Figure 4) shows that the glycoside donor moiety has to be activated using an appropriate activator to form an oxonium ion. The attack of a nucleobase (glycosyl acceptor) may occur on either side of the

• oxonium ion, which can result in two anomers, i.e., an α- and a β-anomer. The factors affecting such stereocontrolled glycoside bond formations are also discussed in this review. The preparation of the racemate 1c was reported by Belleau et al. in 1989 (Scheme 26) [38]. The method involved the coupling of

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• cyclization of secondary and tertiary l-alkynyl-2,3-epoxyalcohols 131a [94]. This is an example of a Hg(II)-salt-catalyzed rearrangement of 1-alkynyl-2,3-epoxy alcohols to substituted furans. The furan 133a was formed by dehydration of intermediate 132a through the corresponding oxonium cation. When R3 is an

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• oxonium species in the methylation step. Abiraterone acetate (53) is a drug used in cancer treatment [138]. The Mn-catalyzed methylation of an abiraterone analogue was achieved by replacing the fluorination step by mesylation in 15% of overall yield and only a single diastereoisomer was observed (Scheme

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• carbenium ions. Calculations of the isodesmic reactions (1), (2), and (3) demonstrate the overall destabilizing effect of CF3 compared to H or CH3 when directly attached to a carbenium ion (i.e., α position, Scheme 1) [5][29]. Even an oxonium ion appears to be significantly destabilized by the presence of

• ). This dication reacts with benzene to provide pyridinium–oxonium dication 159 in solution. Further arylation does not occur spontaneously, which was evident because alcohol 157 was isolated at the end of the reaction. Upon heating at 60 °C, the second arylation takes place, presumably via the formation

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• relying only on oxonium ions and precursor mass, using a score above 30 were also described recently [15]. A suitable cut-off score should always be carefully evaluated for each (glyco)peptide moiety with respect to the glycoform coverage and accuracy [11]. Byonic identified the relevant N-glycosylation

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• complex intermediate C. C is subjected to the nucleophilic attack of n-butyl vinyl ether (140) and generates alkenyl metallic intermediate D. Intramolecular nucleophilic attack onto the oxonium carbon of D affords the [3 + 2] cycloaddition product 141 with regeneration of the catalyst A. In 2020, Ye and co

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• conversions, computational and experimental data indicated that the protonated hydroxy groups (oxonium ions) are not persistent intermediates, but rather cleavage of the carbon–oxygen bond is almost instantaneous [12]. It is assumed that ionization to the carbocations occurs in a stepwise process, first

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• ]. Subsequent oxidation of radical 7 by Cu(II) affords a formally cationic intermediate that is trapped by the carbamoyl oxygen to afford oxonium 8. The loss of the tert-butyl cation provides the oxyamination product 2, which can be isolated in good yields with excellent diastereoselectivity. Turnover of the

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• formed. An ipso-cyclization with aromatic ring occurres and gives the intermediate 61 when R1 is a para-methoxy group. The oxonium ion 62 is produced by the oxidation of the intermediate 61 under the action of Fe3+ [81]. Lastly, the oxonium ion 62 is transformed into the desired product 56 in the

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

• the yields and the enantiomeric excess. In a third reaction, the 1,4 addition of silyl keten acetals 11 to chromone 20 is investigated (Table 11, Scheme 8). Chromone 20 is first transformed to the oxonium ion pair 21. Catalyst BIFOXSi(OH)2 (9) binds the triflate anion via hydrogen bonding and leaves

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

• replacement of carbon atoms by the heteroatoms oxygen, nitrogen and sulfur, respectively. Thus, “oxacarbenium ion” would denote a carbenium ion whose carbon atom is replaced by an oxygen atom, that is, an oxonium ion (3; Figure 2). Although if a coherent structure by formal subtraction of hydride from the

• term “carboxonium ion” to describe intermediates 1. The issue with this term is that it is used for many different oxonium ions independently of their structure, mainly intermediates with a variable number of oxygen atoms bound to the central carbon atom. This name is used to describe protonated

• carboxylic acids (carboxylic acidium ions), protonated esters and protonated aldehydes and ketones amongst others [31]. The name thought to be originated from the combination of the terms “carbenium” and “oxonium”, but not correctly applied to such a broad scope of intermediates. Clearly the intermediates

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• under liberation of a chloride. For the formed oxonium ion, two conformers A and B are possible due to free rotation around the single bond neighboring the SF5 group and the former benzylic carbon atom (Scheme 4). Due to the possible repulsive interaction of the SF5 group with the quinoid ring in

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• domino reactions of diazo compounds with intermediate formation of ylides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Thus, it was for example shown that ammonium or oxonium ylides generated in the course of intermolecular processes can be easily trapped by ketones, imines, α,β-unsaturated

• examples of such reactions are for instance syntheses of multisubstituted indolines [23][24][25], pyrrolidines [26][27][28][29], dihydropyrroles [29], tetrahydrofurans [27][28], and 2,5-dihydrofurans [31][32], which proceed as intramolecular interaction of generated ammonium or oxonium ylides with carbonyl