Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• diphosphate (E,E-FPP) as their linear precursor (Scheme 1). The 6,7-bond formation was triggered by eliminating the pyrophosphate group of E,E-FPP yielding a monocyclic carbocation intermediate A, followed by the 6,11-closure via deprotonation to afford bicyclogermacrene (B) containing a gem

• -dimethylcyclopropyl unit [28]. Bicyclogermacrene (B) served as the branch point of aromadendrane cyclization and aristolane cyclization routes (Scheme 1, I). On one hand, the protonation on the double bond Δ1,10 of B initialized the aromadendrane cyclization, followed by 1,5-bond formation to yield carbocation

• intermediate C. Firstly, deprotonation occurred to form the double bond Δ1,10 and led to the formation of (−)-ledene (D) [29], on which the multiple-step oxidation happened at C-2 and C-9 to generate (+)-1. Secondly, the reaction is quenched by an H2O attach at carbocation C-10 to form (+)-globulol (E) [30

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• cyclase) act on geranylgeranyl diphosphate (GGDP) to perform regio- and stereoselective cyclizations or skeleton rearrangement reactions via carbocation chemistry to form diverse and versatile carbon skeletons; and ii) multiple post-modification enzymes, most often cytochrome P450s, decorate the carbon

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• the water addition occurs on the C3' carbocation, which is generated by one electron transfer to the ferric iron from the C3' radical intermediate (carbocation mechanism in Scheme 9). Notably, in this last step, the stereochemistry of the hydroxylation reaction is regulated by the enzyme to be the R

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• carbanion I that is solvated by the polar solvent. The carbanion I then adds to the carbon (carbocation) of the nitrile oxide, to give the intermediate II. Due to steric effects, the intermediate II undergoes bond rotation to the lowest-energy conformation II-D in which the methyl group is at a close

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• subsequent water elimination leading to a stable tertiary, bis-benzyl carbocation that evolves forming the corresponding alkene by proton elimination (Scheme 3). The reaction was carried out at 60 °C with 10 mol % of 16 (Table 2, entry 1), monitoring the formation of the products by 1H NMR and GC–MS (see

• carbocation species. It has also to be considered that water elimination during the progress of the reaction changes the ratio between capsules A and B thus accelerating product formation. The intrinsic stability of the carbocation formed by water elimination from the corresponding alcohol is crucial to

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• SO2Cl− ion or as SO2 + Cl−) (Equation 5). It would be of interest to extend this study to other RSO2Cl substrates, where the R forms a relatively stable carbocation, such as the 1-adamantanesulfonyl chloride and/or the diphenylmethanesulfonyl chloride [(C6H5)2CHSO2Cl], examples with intermediate cations

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen. The nucleophilic attack of 2-arylaziridine 2 on the ketene moiety produces zwitterionic intermediates B, in which the aziridinium is opened to form the benzylic carbocation stabilized through the

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

• oxidative addition, transmetallation, and reductive elimination processes. On the other hand, iron may act as a Lewis acid, activating carbon–carbon multiple bonds via π-binding or heteroatoms via σ-complexes. This can either generate the organoiron complex after nucleophilic attack or produce a carbocation

• alkyl cation 113. Nucleophilic trapping of the carbocation provides the final product. In 2018, the Li group continued to explore Fe-catalyzed silylation cascade chemistry. Their protocol investigated the silylperoxidation of activated alkenes in good yield [107]. In 2019, Yang and co-workers described

• radical across the alkene to afford the benzylic radical. Oxidation of the corresponding radical affords the benzylic carbocation which is attacked by the indole nucleophile. The authors applied the reaction methodology to pyrrole as a substrate; however, only one example was given in a 50% yield. Further

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• -naphthol (88) and allene-iminium intermediate I-24 to form axially chiral I-25, followed by rearomatization of the naphthol ring of I-25 and isomerization to I-26. Thereafter, CPA forms two hydrogen bonds with the two OH groups of I-26 to generate a carbocation and facilitates an intramolecular

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• and pinacol/semipinacol rearrangements, the 1,2-shift does not require a leaving group or carbocation intermediate, as the neighboring π system is capable of accepting the migrating group. While the reaction is generally reversible, the product can be favored through four common strategies: (1) the

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

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

• Hg(TFA)2 then five- and six-membered rings 64 and 65 were formed with a 1:4 ratio (Scheme 22) [70]. The greater yield of the six-membered product was primarily due to the electron-withdrawing effect of ethereal oxygen which in turn destabilizes the carbocation at the β-carbon and hence the

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• -3-yl) phosphate 2 is activated by protonation with a haloid acid. Subsequently the phosphate leaving group is eliminated to generate the carbocation intermediate III, which is then followed by rapid combination with a nucleophilic halide ion to form a 3-monohalooxindoles 3 or 4. Conclusion In

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• synthesis is based on the o-quinone methide intermediate [54][55][56][57][58]. The carbocation formed by the activation of an alkene with acid turns into an intermediate o-quinone methide, resulting in a successful cyclization. As seen in the mechanism, the acid catalyst adds to the vinyl group, allowing

• the formation of a tertiary carbocation. The carbocation is then transformed into the o-quinone methide intermediate, which undergoes cyclization to yield 9-methyl-9-arylxanthene by aromatization. When the yields of the synthesized compounds are examined, it is seen that the yields are high when there

• is no substituent at the ring to which the carbocation is attached or when there is an electron-donating group, such as a methoxy or methyl group (Figure 1). When there are electron-withdrawing groups, such as chlorine or cyano groups, in the ring, the yield is slightly reduced because they

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• C, which undergoes an oxidation process to generate carbocation D. A proton abstraction from D then affords the observed product. Cross-coupling reaction between unactivated olefins and alkyl halides under nickel catalysis The use of alkyl halides in transition-metal-catalyzed cross-couplings to

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• intermediate or arenium ion 7 (Scheme 2). This occurs at the bridge as this offers greatest release of strain energy. Rearrangement to 8, as described by Cram and Hefelfinger, further lowers the strain energy of the cyclophane [36]. The carbocation could be trapped by a nitrate anion to give intermediate 9

• , which would collapse to the dienone 10. Tautomerization results in regeneration of the aromatic ring in 11. Such a route might explain the unique ability of nitration conditions to deliver the substituted [2.2]metaparacyclophane. Alternatively, carbocation 8 might be trapped with water and, under the

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

• intermediate 6 then would undergo a Prins-type intramolecular cyclization with the olefinic bond to produce a stable benzyl carbocation 7, that may be trapped through a Friedel–Crafts alkylation with an aromatic substrate or through the reaction with an external nucleophile to afford the target product 8

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• carbocation species [52]. Thus, in contrast to the other primary alcohols, an excess of 3.0 equiv was required to provide a moderate 62% yield of mannoside 3g when benzyl alcohol (2g) was used as an acceptor. Next, the formation of tertiary carbenium ion from 3-methyl-butan-2-ol (2i) via 1,2-hydrogen shift in

• an initial formed secondary carbocation [52] explains the relatively low yield of mannoside 3i. The same problem was observed when 1-adamantanol (S5) was used as a glycosyl acceptor and the desired mannoside was formed in only 6% NMR yield (Figure S1, Supporting Information File 1). Finally, a

• mixture of mannosides α-3r and α-3s was obtained when cyclopropylmethanol (2r) was applied. The cyclopropylmethyl carbocation (C4H7+), which is generated in liquid SO2 medium, can undergo a rearrangement to form a cyclobutyl carbocation [68]. The latter can be trapped by a water molecule forming

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

• and co-workers explained the formation of all-cis-2,4,6-trisubstituted THPs with the help of density functional theory (DFT) and stated that in the presence of an external nucleophile, the stabilization of the carbocation intermediate is favored through hyperconjugation [28]. The vacant p-orbital of

• alkoxycarbenium ion intermediate 282, which is followed by a sequential cyclization to form secondary carbocation 283, which in the presence of fluoride ions affords 284, as shown in Scheme 66. Banerjee et al. explored the reactivity of cyclopropane carbaldehydes 285 with 3-butyn-1-ol in the presence of TiX4 for

• subsequent trapping of the carbocation with the bromide ion led to all-cis-2,4,6-trisubstituted tetrahydropyran 297 (Scheme 69). Lalli and van de Weghe reported a chiral BINOL-derived bisphosphoric acid- and CuCl-catalyzed enantioselective tandem Prins–Friedel–Crafts cyclization between homoallylic alcohol

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• 5m compared to the longer chain substrates (e.g., 5c and 5l) could be explained mechanistically by the formation of a terminal carbocation upon the extraction of a fluorine atom by the aluminium species (Scheme 3). This carbocation could be stabilised to varying degrees by the ketone moiety

• mass spectrometry and so it was converted to carboxylic acids 14 and 15 by the treatment with silica gel and NaOH, respectively, in order to confirm its identity. A possible mechanism for the formation of 13 from 5n could involve the formation of a terminal carbocation from trichloroalkanone 8n

• suggests that the role of the ketone moiety is not only to stabilise the putative carbocation as discussed earlier, but also to deactivate the aromatic ring to Friedel–Craft-type alkylations. However, when the trifluoropentylbenzene 16 was prepared and subjected to the standard AlCl3 conditions (Scheme 6

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

• long been investigated. This review highlights recent and past reports focusing on their study and potential in modern synthetic transformations. Keywords: carbocation; organic synthesis; superelectrophile; trifluoromethyl; Introduction Carbocations are pivotal intermediates in organic chemistry, and

• carbocation-based synthetic chemistry continues to be a vital part of industrial and academic chemistry [1]. A countless number of carbocations have been generated and studied [2][3], and many famous organic chemists strongly participated in their development. Carbocations that are especially intriguing are

• cations is probably the α-(trifluoromethyl) carbocation. Many efforts are currently devoted to develop methods allowing the efficient insertion of fluorine atoms or fluorinated groups into organic molecules [7][8][9][10][11][12]. The increasing demand for fluorinated scaffolds, due to the striking

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

• isopropanol as reductant, in conjunction with a Noyori–Ikariya ruthenium-based homogeneous catalyst (Scheme 36) [73]. 2 Reactions of difluorocyclopropane and its derivatives Difluorocyclopropanes are synthetically useful substrates for a variety of reactions such as thermal rearrangements, carbocation

• in 105, which is associated with a difference in the regioselectivity of the C–C bond cleavage. The dissociation of the tosylate 104 to generate a cyclopropylmethyl carbocation A was accompanied by the cleavage of the proximal bond to form homoallylic products. The regioselectivity of the ring

• -fluoropyrroles 142 (Scheme 62) [113]. The reaction involved the gem-difluorocyclopropyl ketones 143 and nitriles 144. It was proposed that the protonation of the ketone with triflic acid led to a partial ring opening of the gem-difluorocyclopropyl ketone to generate a carbocation-like center that was stabilized

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

• tetrachloride produces an alkyoxy allylic carbocation (not shown). This carbocation is subjected to a regiospecific electrophilic substitution of allene 168 to generate a vinyl cation 172, which is stabilized by an adjacent carbon–silicon bond. The 1,2-shift of the silyl group in 172 produces an isomeric vinyl

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• proposed and is depicted in Scheme 5. Initially, a reaction of 1a and 3a occurred, providing an imine intermediate I, which tautomerized to the corresponding enamine form. Meanwhile, the activation of 2a with AlCl3 allowed the formation of a carbocation intermediate II, which was then trapped by the