HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• limitation, we analyzed the mechanism underlying the formation of resorcin[n]arenes. The first step of the cyclization reaction is a hydroxyalkylation involving various cationic intermediates [69]. Hence, we hypothesized that any factor enhancing the rate of the first step by stabilizing carbocations will

• likely enable new starting materials to be used in resorcin[n]arene synthesis. Since HFIP has recently gained popularity as a solvent capable of stabilizing carbocations in diverse type of reaction settings [70][71][72], we opted to utilize this solvent to overcome the constraints highlighted above

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• benzylic radical furnishing the desired product and regenerating I. Photochemical methods Photochemical methods that make use of fluoride to quench benzylic carbocations in order to form a new C–F bond have proved effective for functionalising a broad range of benzylic substrates. Two concurrent

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

• -covalent interactions plots. Despite the structural similarities between germacrene A and hedycaryol cations, they possess a somewhat different stability trend. These differences are attributed to C+···OH intramolecular interactions present in some hedycaryol cations, which are absent in the carbocations

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• transfer (MH HAT) reactions (Figure 6A). As pointed out by Shenvi in a recent review [11], the major difference between traditional polar hydrochlorinations of alkenes and MH HAT is that the latter is far more chemoselective and proceeds under “milder” conditions. As shown in Figure 7B, carbocations or

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• facile stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles, followed by trapping of the intermediate zinc enolate with carbocations [12]. A practical one-pot synthesis of fluorescent pyrazolo[3,4-b]pyridin-6-ones by reacting 5

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• cyclization reactions involve a number of carbocation intermediates. In some cases, these carbocations are stabilized by through-space interactions with π orbitals. Several terpene/terpenoids, such as sativene, santalene, bergamotene, ophiobolin and mangicol, possess prenyl side chains that do not participate

• hyperconjugative interactions, through-space interactions, and C–H–π interactions, have been intensively investigated by Tantillo and co-workers, who have contributed greatly to revealing the intriguing nature of carbocations [7][19][20]. We have also elucidated various new insights of carbocation chemistry, such

• carbocations, which we recently discovered, reactions with activation energies around 16 kcal/mol have been reported [22]. In the pathway shown in Figure 1, the highest energy barrier was 14.6 kcal/mol. Conversely, in Figure 2, path a had an energy barrier of 9.9 kcal/mol and path b 13.6 kcal/mol. From these

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• -4,4,4-trichloro-3-hydroxybutan-1-ones; ArCOCH2CH(OH)CCl3) undergo dehydration to the corresponding CCl3-enones, which are further cyclized into CCl3-indanones. The yields of CCl3-indanones starting from CCl3-hydroxy ketones are up to 86% in TfOH at 80 °C within 3–18 h. Keywords: carbocations; enones

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• 10.3762/bjoc.19.65 Abstract We present here a stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. The use of a chiral NHC ligand provides chiral zinc

• , imines, other Michael acceptors, or alkyl halides. Our group is developing trapping of metal enolates with stabilized carbocations and could show that magnesium enolates generated from enones [22], unsaturated amides [23], or heterocycles reacted with tropylium, dithiolylium or flavylium cations [24

• a tandem reaction comprising the Cu–NHC-catalyzed addition of dialkylzinc reagents to enoyl imidazoles followed by a trapping reaction with various onium compounds (Scheme 1). In this work we show the development of this methodology and its application to a range of acylimidazoles and carbocations

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• rearrangements, as postulated by Novitskiy and Kutateladze do not occur spontaneously from neutral compounds without the intermediacy of carbocations. As it turns out, compound 3 in the authors’ scheme is one of the products we described in our original manuscript and is perfectly stable thermally and does not

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , and Mannich-type reactions, Michael addition, nucleophilic substitutions, cyclopropanations, and reactions with carbocations. The field of asymmetric conjugate addition with its extension into enolate trapping reactions began to develop approximately in 1996. In this review article, we analyze more

• Lewis acid-mediated generation of magnesium enolates in the trapping reactions with carbocations. Indeed, unsaturated amides, alkenyl heterocycles, or even unsaturated carboxylic acids successfully participated in this process affording structurally interesting products (Scheme 26) [63]. Apart from

• carboxylic acids [64], we have attempted a similar trapping reaction here as well. Gratifyingly, the corresponding trapping products 106 could be isolated with tropylium and benzodithiolium cations (Scheme 27B). We have continued our exploration of enolate reactions with carbocations by studying the trapping

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

• “Synthèse Organique”, 4 Rue Michel Brunet, 86073 Poitiers Cedex 9, France 10.3762/bjoc.17.32 Abstract “The extraordinary instability of such an “ion” accounts for many of the peculiarities of organic reactions” – Franck C. Whitmore (1932). This statement from Whitmore came in a period where carbocations

• began to be considered as intermediates in reactions. Ninety years later, pointing at the strong knowledge acquired from the contributions of famous organic chemists, carbocations are very well known reaction intermediates. Among them, destabilized carbocations – carbocations substituted with electron

• -withdrawing groups – are, however, still predestined to be transient species and sometimes considered as exotic ones. Among them, the CF3-substituted carbocations, frequently suggested to be involved in synthetic transformations but rarely considered as affordable intermediates for synthetic purposes, have

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• mediated by strong acids led to the cleavage of the proximal bond by the generation of fluorine-stabilized carbocations (SN1 mechanism) [114]. The Friedel–Crafts reaction of 2,2-difluorocyclopropanecarbonyl chloride (148) with arenes 149a–c was accompanied by a proximal bond scission promoted by the strong

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• emerged that the 1,2-hydrogen shift in TS7 is quite high in energy (ΔG‡ = 18.5 kcal⋅mol−1) relative to the previous barriers shown in Figure 2. This barrier is also much higher than the traditional 1,2-hydride shift in carbocations, which usually show barriers even under 10 kcal⋅mol−1. It has been

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• case of [PF6]–-salts while no issues have been reported for the aluminate [6]. The oxidized intermediate PA+• (Equation 7) forms the conjugate acid by decomposition of this instable intermediate resulting in nucleophilic photoproducts inhibiting ring opening polymerization mechanism where carbocations

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• energetics using QM calculations in an active site cluster model. The active site cluster theozyme model [43][44] was constructed from the crystal structure coordinates of active site amino acids, which were presumed to stabilize the carbocations during the reaction cascade. Each reaction step's relevant

• interactions with N103, I181, and W186, which likely made similar stabilizing contributions as in cation H. It is well established that the inherent reactivity of carbocations [27], as well as correct substrate folding in the active site [3], play crucial roles in terpene synthases. The current results

• and co-workers [39]. The amino acid cage was constructed from six amino acids, which were located around the substrate and constituted part of the catalytic pocket of the enzyme (PDB-ID 6GGI) [42]. The chosen amino acids were the ones that we presumed stabilized the carbocations the most during the

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• the leaving pyrophosphate group and the nucleophilic alkenes in proximity to initiate the C–C-bond forming, carbocation-mediated cascade reactions [10]. The hydrophobic binding pocket stabilizes the reaction intermediates and tames the propagation of carbocations through cation–π and other

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• . This supports thermodynamic control based on carbocation energies. Keywords: arenium ion; carbocation; density functional theory; microwave reaction; rearrangement; superacid; Introduction Carbocations are enigmatic reactive intermediates of enduring importance in chemistry. No other reactive species

• arenium ions, like many other types of carbocations, often rearrange by 1,2-shifts. This leads to a fascinating collection of rearrangements that can migrate hydrogen, halogens or more complex substituents around the ring and even modify the carbon skeleton. Early reports by Baddeley [18] helped to

• . Common to both potential energy surfaces are the lowest energy non-ipso carbocations 12a–17a which lie at the bottom on the energy scale. It is noteworthy that m,p' cation 13a is the lowest energy species predicted by our calculations. In each diagram, double-headed vertical arrows show the energy

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• dogmatic dispute in the TPS community about the respective roles of the protein acting as a scaffold and the “inherent” carbocation reactivity [91] in orchestrating an enzyme specific reaction cascade. With regard to the latter, the “inherent reactivity” of carbocations is no doubt an important ingredient

• role of the enzyme environment in guiding the reaction cascade [94][99][100][101][102]. In case of CotB2, mutagenesis studies of plasticity residues of CotB2 [30][36][37][38] have been demonstrated to drastically change the propagation of the carbocations and consequently alter the product portfolio

• that this plasticity of side chains in the active site of CotB2 plays not only an important role in stabilization and hence propagation of carbocations. In future experiments, it would be interesting to investigate the influence of double or triple mutations within the active site. Moreover, it would

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• energetics of possible carbocations. Furthermore, it is possible that γ-cadinene is formed via (R)-(+)-germacrene D. Yoshihara et al. showed that isolated germacrene D reacts to β-bourbonene by irradiation with intense UV light (Hg lamp) [35]. However, the formation of β-bourbonene in plant cells by this

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• ; rearrangement; silicon; Introduction Carbocations, positively charged trivalent carbon compounds and reactive intermediates, have continued to fascinate chemists since the early discoveries of tropylium [1][2] and trityl [3][4][5][6][7] salts. Many of the giants of organic chemistry during the last century

• contributed heavily to the development of carbocation chemistry. This article will deal with three types of carbocations that have been of intense and fundamental interest over the years, i.e., cyclopropylcarbinyl cations, electron-deficient cations, and silyl substituted carbocations. A brief overview of

• these types of carbocations is warranted. Cyclopropylcarbinyl cations are an extensively studied system [8][9]. Initial interest was derived from the fact that both cyclopropylcarbinyl and cyclobutyl substrates 1 and 2, where X represents diazonium ion [10][11], chloride [10], or naphthalenesulfonate

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• carbocation. In the case of pyrrolidines, the carbocation is completely stabilized as an energy minimum in the form of an iminium ion and the reaction takes place in two steps. Keywords: alkanes; carbocations; DFT; oxidations; ruthenium tetroxide; Introduction Ruthenium-catalyzed oxidations [1][2] and, in

• -mediated oxidation of tertiary amines [26] by trapping them with cyanide anion [27][28]. These results point out the formation of transient carbocations III that can be stabilized by the presence of heteroatoms in the alpha position. The formation of transient carbocations do not contradict, necessarily

• can lead to different products in a ratio that depends on reaction dynamics [31][32][33]. The study of molecular dynamics trajectories has allowed characterization of ambimodal transition states in reactions involving carbocations [34][35]. We have demonstrated computationally the presence of

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

• from diol 9. Proposed mechanisms leading to products 10 and 11. Products and relative yields from the reaction of alcohol 18 with CF3SO3H and C6H6 [12]. Comparison of superelectrophilic carbocations (3–5 and 14) and their chemistry. DFT calculated relative energies of pentacations 16 and 21 [14

Cyclobutane dication, (CH₂)₄²⁺: a model for a two-electron four-center (2e-4c) Woodward–Hoffmann frozen transition state

• G. K. Surya Prakash and
• Golam Rasul

Beilstein J. Org. Chem. 2019, 15, 1475–1479, doi:10.3762/bjoc.15.148

• carbocations, could not be interpreted by the classical tetravalency bonding concept [2][3] also requiring the engagement of a 2e-3c bond as suggested by Olah in 1969 [4][5]. A compelling number and huge array of carbocations involving higher coordinate carbon is by now realized by experimental studies

• . Hypercarbon chemistry covers in addition to carbocations also carboranes, carbon-bridged organometallics, carbonyl clusters, along with others. The rapidly evolving field has been extensively surveyed [6]. In comparison, structures of the carbocations involving a two-electron four-center (2e-4c) bond are rare

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• synthesize stabilized chiral carbocations with chirality installed onto their backbones. Pioneering efforts along this line by Kagan, Sammakia, and Chen have shown that chiral catalysis with such chiral carbocations was indeed plausible to achieve stereocontrol (Scheme 1a). [14][15][16][17][18][19]. However

• with weakly coordinating metal-based phosphate anion. a) The reaction with 9,10-dimethylanthracene (3b). b) Gram-scale reaction of 3a and 4k, and transformation of cycloadduct 5k. Screening and optimization for the asymmetric catalyzed Diels–Alder reaction of anthracene by carbocations. Scope for the

• asymmetric catalyzed Diels–Alder reaction of anthracene (3a) with ketoesters 4 by carbocations. Supporting Information Supporting Information File 282: Experimental procedures and characterization data of all products, copies of 1H and 13C NMR, IR, HRMS, and HPLC spectra of all compounds. Acknowledgements

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• enzymatic step [1][2][3]. With this approach, nature makes perfect use of the versatile chemistry of carbocations with its hydride or proton shifts and Wagner–Meerwein rearrangements leading to a large variety of possible structures. Among terpenoid natural products, achiral compounds are rarely found, but