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 of (S,S)-carveol-derived TBS ether 163b with triethylborane (Scheme 31). This reaction proceeded with isomerization and formation of the intermediate carbocation 181, which underwent 1,2-carbon migration to form the cyclopentane product 182. A sequence of oxidations of borane 182 with

• form three possible products: ketone 191, olefin 192, and cyclopentane 193 (Scheme 33). At the first stage, the epoxy ring was opened to form intermediate A. According to the authors [87], there are three possible ways of carbocation stabilization. The 1,2-shift of a proton at C3 to C4 led to the

• reaction proceeded through the formation of intermediate carbocations B and C. The cyclopentane derivative 194, annelated with cycloheptanone, was obtained from carbocation C. As a result of the reaction, the C10 atom underwent migration, which led to the expansion of the cyclopentane ring. Compound 195

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• mechanism involving single-electron oxidation of an enamine intermediate, addition of the resulting radical to the olefin, single-electron oxidation of the adduct to form a carbocationic intermediate, and intramolecular nucleophilic attack on the carbocation to form the pyrrolidine ring. The reaction

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• , whereas internal alkynes favored the 8-endo-dig pathway due to steric constraints and carbocation stability. This strategy facilitated efficient and selective synthesis of macrocyclic amines, with precise ring size control via substituent modulation. In 2021, Liu group reported a BiCl3-mediated

• (Scheme 23) [34]. When the Ph3PAuCl/AgBF4 system was employed, the alkyne underwent an intramolecular nucleophilic attack by the C-3 position of indole to form a carbocation intermediate 112. This intermediate underwent a Wagner–Meerwein-type 1,2-alkyl migration, ultimately leading to the construction of

• controlled synthesis of nitrogen-containing heterocycles via reaction pathway modulation (Scheme 32) [45]. Under catalysis of Cu(OAc)2 and HOAc, the substrate was subjected to decyanation and followed copper-promoted [2 + 2] cycloaddition that yielded cyclobutene intermediate 155. Carbocation rearrangement

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• aldehyde 3. This linear aldehyde would be activated by an acid to trigger a key Prins cyclization with the trisubstituted olefin through reaction model 3 and generate a putative tertiary carbocation to be trapped by the chiral alcohol, providing bicycle 4 stereoselectively. Finally, the last olefin would

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

• challenging amines. The combination of simple reaction conditions and excellent chemoselectivity makes this protocol very robust and suitable for both the academia and industry. Kinetic and computational experiments support an SN1 mechanism via loss of sulphur dioxide and oxetane carbocation formation. Two

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

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• hydroperoxide transfer from copper complex D with the formation of intermediate H and, therefore, regenerating Cu(I) B. Alternatively, the latter can be formed by oxidation of benzylic radical G with the formation of carbocation I. However, given that in the absence of oxygen the β-ketophosphonate was formed

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

• trimethylsulfoxonium iodide (TMSOI) with DMSO-d6, resulting in CH3/CD3 exchange. Furthermore, Chisholm and co-workers (2019) synthesized bulky cinnamate esters 61–64 utilizing a trichloroacetimidate-based alkylating agent in moderate to excellent yields via carbocation 65 formation upon trichloroacetamide release

• -workers (2019) employed a non-metal Lewis acid tritylium salt (TrBF4) to catalyze the stereoselective olefination of α-diazocarbonyl compounds 438 to access Z-cinnamate esters 439–442 via 1,2-hydride migration (443) (Scheme 89) [151]. The ion pair of carbocation, BF4− anions, and the trityldiazene group

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

• tetrahydropyran-containing amino acid derivatives via anodic decarboxylation of N-acetylamino malonic acid monoesters to generate a stabilized carbocation (Hofer–Moest conditions), which were then reacted with a tethered oxygen nucleophile [4]. In this follow-up study, we demonstrate that N-protected amines are

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

• the alkene moiety of the amine. The resulting stabilized carbocation 15 is then captured by formaldehyde (generated in situ from DMSO) leading to an intermediate oxocarbenium 16 that undergoes a cyclization to obtain the sulfenylated oxazinane derivative 13. In isotope labelling experiments using DMSO

• of an N–C bond, where the stability of the leaving carbocation is the main factor that affects the rate of this step. Next, intermediate 37 is attacked by the phosphorus compound, giving product 35 with retention of the configuration. This mechanism was confirmed when compound 36a was isolated as

• product 35b was obtained, confirming that the dihaloalkane compound is the source of the methylene unit (Scheme 28c). Depending on the stability of the leaving carbocation, the selectivity of the R–N cleavage follows the decreasing order for the R groups: H, t-Bu, allyl, benzyl > methyl > primary

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

• the inversion at the anomeric sp3 carbon centre by the attack of the acceptor moiety. Crich β-mannosylations are classic illustrations for the same [38][39]. On the other hand, the stability of the carbocation contributes towards the reaction to proceed via the dissociative two-step SN1 reaction

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

• the allyl carbenium ion VI through the loss of a molecule of water, then undergoes a Friedel–Crafts alkylation by attack of the aromatic partner. The outcome of the reaction proceeds through a Markovnikov protonation of the allylated arene VII by triflic acid, which generates the carbocation

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

• molecule of TBHP is oxidized by Fe(III) into tert-butylperoxy radical B. Radical A abstracts a hydrogen atom from ether 78 to give the C-centered radical C. The authors propose two further pathways for the formation of the target product 79. Pathway I: The C-centered radical C is oxidized to carbocation D

• ), abstracts hydrogen atom from silyl allene 122 to form the C-centered propargylic radical B. Fe(III) oxidizes radical B to carbocation C which reacts with Fe(III)OO-t-Bu complex D to yield the target peroxide 123. Cyclopropanols 124 [101] and their derivatives 128 [102] were used as a source of alkyl moiety

• final peroxide 157: recombination of radical C with tert-butylperoxy radical D or oxidation of radical C to carbocation E, which is nucleophilically attacked by TBHP. β-Peroxy ketones 159 were synthesized via oxidative dimerization of styrenes 158 using the Cu(I)/TBHP system (Scheme 50) [42]. The

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• carbocation intermediate, which rearomatizes through proton loss. Concurrently, the cathodic reduction of the generated protons produces H2. In addition to (hetero)aromatic groups, alkene scaffolds also underwent this reaction (Scheme 3). In the same year, the Lei group [10] extended the electrochemical C(sp2

• . Mechanistically, this transformation can be understood as follows: first, a Br/Cl/CF3 radical is formed via anodic oxidation, which subsequently attacks the olefin. The newly formed benzyl radical is oxidized to a carbocation, which undergoes nucleophilic attack by DMF. Hydrolysis of the imine delivers the final

• oxidized to a carbocation, which is subsequently attacked by the alkoxide to furnish the final product (Scheme 17). The Lei group also demonstrated C–F-bond formations, particularly developing an electrochemical method for the cleavage of C–C bonds and the 1,3-difunctionalization of arylcyclopropanes [26

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• one diastereomer of 7q was formed (Scheme 4). This result is in accordance with the calculated mechanism. The more electron-rich trisubstituted alkene 3r reacted directly with Selectfluor leading to a tertiary carbocation which was trapped by acetonitrile in a Ritter-type process to generate bisamide

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• -disubstituted olefins is observed and interpreted as evidence that aziridination proceeds via a carbocation intermediate that subsequently cyclizes. These results demonstrate a simple method for activating iminoiodinane reagents, provide analysis of the extent of activation achieved by H-bonding, and indicate

• iminoiodinane reacts directly with the olefin to generate a short-lived alkyl-bound iodinane 7 or iodonium species 8 (Scheme 4f). Ligand coupling from 7 or extrusion of iodobenzene from 8 would furnish a carbocation intermediate 9 which could undergo C–C bond rotation prior to ring closure to form the aziridine

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• electricity was passed to the solution. A plausible reaction mechanism for the current reactions is described in Scheme 3. The reaction of carbon–carbon triple bonds and H+ species, which are derived from the Brønsted acid (in method A) or EGA (in method B), gives the vinylic carbocation intermediate A, which

• can react with BF4− to give fluorinated alkene B [57][58][59][60]. In the next step, B can undergo the second addition of H+, followed by the incorporation of F− into the carbocation intermediate C, forming the difluorinated compound 2a. The carbocation adjacent to the F atom might be stabilized by

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• above and on literature precedents [40][41], a plausible mechanistic pathway for the formation of 2 and 3 is shown in Scheme 5 (with the reaction of 1a as an example). In the presence of DBSA, the protonation of 1a results in the carbocation intermediate I. Then, the nucleophilic attack of H2O at the

• carbocation of I produces intermediate II, which converts into intermediate III through a deprotonation–protonation process. Finally, the elimination of PhNH2 from intermediate III occurs to afford the desired product 2a. In the presence of NaOH, the Michael addition between 1a and base initially occurs to

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• primarily resulted in the formation of isomers 74, in which the positive carbocation of the ylide was attacked by the double bond of methylene (C-161), followed by the addition of the negative oxygen atom of the dipole. This cycloaddition occurred highly selectively on the α-side of the double bond. Minor

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• skeletal rearrangement, providing the distinct skeleton of 11 via carbocation C. This rearrangement involves the preferential migration of an alkenyl group in C to the carbocation, followed by deprotonation at C18 to form an exo-olefin. β-face-selective hydroxylation at C12 in 11 by the P450 enzyme BscG

• in unexpected conversions, including the formation of an allylic carbocation at C1, followed by transannular hydride transfer from C8 to afford ketone 20 in 62% yield. With the 5/8/5 tricyclic scaffold 20 in hand, site- and diastereocontrolled C9 hydroxylation of 20 produced a substrate 21 for the

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• and 30). In these cases, a carbocation-involved pathway may be operative to yield the product. The successful and exclusive observation of product 29, however, provided a piece of evidence to the objection of this possibility, as no carbocation-based rearrangement product was observed in our reaction

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• selectfluor and a carbocation is formed by bonding with fluorine. Subsequently, fluoroalkoxy compound 4 is formed by Wagner–Meerwein rearrangement followed by alcohol addition and deprotonation. Conclusion New bicyclic fluoroalkoxy compounds were synthesized by a molecular fluorine and metal-free methodology

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• side products is proposed through path b (Scheme 3). The elimination of α-proton on the side chain of dialkyl bromoalkenes results in iodonium intermediate D, which on the expulsion of PhI gives a mixture of the allylic carbocation E, which ultimately gets trapped by MeCN in the presence of H2O, giving

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• the germacrene A and hedycaryol-derived carbocations. This study focused on twelve hydrocarbons derived from germacrene A and twelve from hedycaryol, which can be divided into three groups: four molecules containing 6-6 bicyclic rings, four 5-7 bicyclic compounds with the carbocation being on the

• seven-membered ring and the remaining four 5-7 bicyclic compounds with the carbocation on the five-membered ring. The variations in energy within the groups of carbocations (i.e., 6-6 and two kinds of 5-7 bicyclic carbocations) can be ascribed to intramolecular repulsion interactions, as seen from non

• derived from germecrene A. Keywords: carbocation; germacrene A; hedycaryol; stability trend; terpenes; Introduction Terpenoids form a large and highly diverse group of natural products with a wide range of usage in the pharmaceutical, cosmetic, agricultural, food, and energy industry. Among their

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• they often synthesize multiple products from a single substrate through complex cyclization cascades [4][5][6][7][8][9][10]. Based on the mechanism of initial carbocation generation, TSs generally fall into two main classes. Class I TSs generate an allylic cation from a prenyl substrate by

• depyrophosphorylation, whereas class II TSs utilize a general acid (a key Asp residue) to protonate the terminal C=C bond or epoxide group to yield a tertiary carbocation. The highly reactive carbocation is then converted to different carbocation intermediates, facilitated by the hydrophobic pocket of the TSs, which