New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• (NIS) in nitromethane. The resultant carbocation-like species presumably underwent a 1,2-alkyl shift to provide a silylated oxocarbenium ion. The following silyl cation trapping with a bromide anion resulted in 2-phenylcycloheptanone. When a chiral substrate (59% ee) was treated with NIS, a product

• with significantly lower ee (11%) was observed. These results suggest that the reaction might proceed mainly in a stepwise SN1-like manner, via a benzylic carbocation intermediate. Despite the fact that several variants of chiral halogen bond-donor catalysts have been synthesized, to the best of our

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• group of 5 and/or 9, leading to the formation of a stable 3°carbocation that can undergo further dehydration reactions until full aromatization to the naphthalene ring is achieved. This study would serve to help us to find the real scenario. Finally, in the presence of Lewis/Brønsted acids, substrates 6

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• rate on the stability of the intermediate carbocation is even more evident in the series of primary benzylic alcohols. Among them only the p-methoxy-substituted compound 1c shows high activity. In particular, with thiol 2e some ether was formed that during time is converted into the product (Table 2

• , entry 15 and Figure 5). On the other hand highly hindered alcohol 1g with a tertiary carbinol atom gave a very fast and selective reaction (Table 2, entry 11). Thus we can conclude that the reaction rate follows the carbocation stability according to an SN1 mechanism. To confirm this hypothesis the

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• previous analogous reactions, a relatively stable carbocation intermediate was more likely to have formed in this aminochlorination reaction (Scheme 6). Moreover, when the carbocation intermediate was formed, strong electron-withdrawing groups at the phenyl ring in the 3-position of the carbocation are

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• hydrophobic cavity from which water is excluded to enable carbocation chemistry in an aqueous environment. Furthermore, the hydrophobic cavity provides a template that arranges the substrate in a certain conformation to determine the formation of a specific product. Single residues such as phenylalanines are

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• improved orbital overlap. Protonation of the hydroxy group of 9 under the reaction conditions likely leads to the corresponding tertiary carbocation under equilibrium. The nitrogen lone pair can then assist the electrophilic cyclisation reaction, augmented by improved orbital overlap with the aromatic π

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• feature of the Criegee rearrangement is that the Criegee intermediate rearranges into a carbocation. The mechanism of the Criegee reaction is presented in Scheme 38. Initially the reaction of the peracid with the tertiary alcohol 122 produces perester (Criegee intermediate) 123. One alkyl substituent

• migrates from the carbon atom to the adjacent oxygen atom and replaces the carboxylic acid moiety to form carbocation 124. Then, the addition of water to carbocation 124 affords ketone 125 and alcohol 126. p-Nitroperbenzoic acid is usually used to oxidize tertiary alcohols because the anion of this acid is

• the peroxide oxygen atom and the elimination of a water molecule to form carbocation 169. The carbocation 169 is attacked by a water molecule, a proton is transferred to the oxygen atom attached to the phenyl group, and finally the cleavage of the adduct yields phenol (170) and acetone (171). The Hock

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• been proposed in Scheme 6, the reaction can adopt a SET mechanism leading to the intermediate 23a, after C-alkylation. Compound 23a in turn gets converted into intermediate aryl radical 23b. From this intermediate another intermediate aryl carbocation 23c is formed by transferring a single electron to

• the oxidant. Carbocation 23c is stabilized by the amide nitrogen as shown in 23d. Eventually, in the presence of base, rearomatization of 23d takes place to afford the final product of the oxidative coupling reaction. Kündig et al. in their oxidative coupling process using 2.2 equivalent of CuCl2

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• tertiary carbocation is trapped by a gold carbenoid intermediate to form the fused cyclopropane. While there had been reports of utilizing chiral ruthenium complexes for asymmetric catalysis prior to our studies [30][31][32][33][34][35][36][37][38][39][40], there had previously been no reported examples of

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• . The formation of such species from simpler non C=C containing starting materials has been reported and established (1H NMR) by Gopius et al. [52]. Accounting for the exclusive formation of O-acetate rac-83 the trapping of the more stable 2° allyl carbocation intermediate 82 (generated via ring-opening

• of rac-81) with nitrate is preferable to the formation of the higher energy/more unstable 1° carbocation 80 (generated via ring-opening of rac-79, Scheme 13). Subsequent formation of rac-83 allows its hydrolysis with potassium carbonate in methanol to generate the observed rac-16. Isoprene and

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• their characteristics of convertion to vinyliminium species or the delocalized carbocation intermediates in the presence of Lewis or Brønsted acids (LA or BA). In addition to the aforementioned studies on the nucleophilic substitutions, another research focus is the 3-indolylmethanol-based cycloaddition

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• computational study of the likely intermediate suggests that it is best described as a zinc-bound carbocation rather than a zinc carbene (Scheme 12). Notably, Zn is a cheap, earth-abundant 3d metal, thus making it attractive as catalyst for C–H bond functionalization. Conclusion The intermolecular metal–carbene

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout. Keywords: carbocation; density functional theory; dynamics; mechanism; terpene; Review Introduction to terpene forming carbocation rearrangements Terpene natural products display

• rings that are transformed in only one or two enzyme-promoted reactions. These reactions involve generation of a carbocation by protonation or loss of a diphosphate group followed by cyclization, alkyl shift, hydride shift and/or proton transfer reactions to generate new, more complex, carbocations

• . Ultimately these carbocations are either trapped by a nucleophile (e.g., water, diphosphate) or deprotonated to form alkenes. The details of terpene-forming carbocation cyclization/rearrangement processes have been of interest for decades [1][2][3][4][5][6]. Although much has been learned, new observations

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• spirocyclization of the alkoxy radical D onto the benzene ring affords cyclohexadienyl radical F, oxygenation of which followed by C=O bond formation finally provides the oxaspirocyclohexadienone product 3a. Whereas, the oxidation of the benzylic radical B by the existing Cu(II) species to carbocation G and

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• formation of the stabilized carbocation 11 that may evolve through two pathways. This intermediate may either undergo a ring closure due to the nucleophilic character of the silylated alkyne (pathway A) or react with an oxygenated nucleophile, such as the perrhenate anion, to generate the transient

• isolated. This observation strengthened the hypothesis that the silyl group stabilizes the carbocation intermediate which seems necessary for the cyclization step. Conclusion The discovery of new reaction manifolds often provides a good opportunity to discover novel reactivity in related systems. In this

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• to the carbon atom to generate the most stable carbocation. The most stable carbocation is the benzylic carbocation which would not undergo a rearrangement. As discussed above, when the cyclization reaction of 15 was carried out with [(NHC)AuCl] complexes (Table 1, entry 5), the starting material was

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• ratio of 10:3 (Scheme 7). However, several byproducts were also formed. Voltammetric measurements indicated that the cholesterol oxidation process is controlled by the rate of the electron transfer. It was proven that the oxidation occurs at the allylic position. The C7 carbocation is formed by a two

• cleavage of the C3–O bond in the resulting radical cation leads to the formation of a hydroxyl radical and the steroidal carbocation. Such a mesomerically stabilized homoallylic carbocation can react with any nucleophile present in the reaction mixture. In the absence of better nucleophiles it reacts with

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• carbocation (Scheme 3) [34][35][36][37][38][39][40]. Intramolecular cyclopropanation reactions are often characterized by prolonged treatment with an acid [41][42][43][44][45][46]. Stabilization of the intermediate carbocation by the lone pair of the oxygen atom is enabled by lone-pair conjugation (O-lp

• . Formation of the cyclofenchene derivative 7 is explained by rearrangement via a 2-fenchyl carbocation. The DFT computations of the hydrolysis revealed a higher degree of steric congestion in BIFOP–Cl (1) caused by the fenchane units, relative to the less-shielded and hence much more reactive O–BIFOP–Cl (3

• –BIFOP–H (4), O–BIFOP–(O)H (6) as well as diphenyl ether-2,2’-biscyclofenchene 7. Proposed mechanism for the formation of diphenyl ether-2,2’-biscyclofenchene 7 through stabilization of the intermediate carbocation by O-lp conjugation and cyclopropane formation starting from O–BIFOP–Cl (3). The different

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• an intermediate radical cation occurs, thus leading to a mesomerically stabilized homoallylic carbocation and a hydroxyl radical (Scheme 1) [2]. However, the glycosylation reaction was not very efficient due to competition between the sugar alcohol and cholesterol for the carbocation [3]. If

• cyclosteroid (i-steroid) rearrangement is a well-known steroid reaction [6]. The solvolysis of cholesteryl p-tosylate proceeds via the SN1 mechanism with the formation of a mesomerically stabilized carbocation. The addition of a nucleophile (alcohol, water, etc.) may occur either to C-3 or C-6, depending on

• (the kinetic product is formed) since the mesomeric carbocation is more positively charged in this position than in C-3. However, under acidic conditions the reaction becomes reversible and the 3β-substituted product, which is more stable (the thermodynamic product), is exclusively formed. The i

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• that proposed in the study [141]. According to the latter mechanism, the benzylic carbocation rather than benzyl iodide is generated and this carbocation undergoes nucleophilic attack by carboxylic acid. This mechanism is confirmed by the fact that iodide is inert under the reaction conditions. The

• hydrogen atom from the benzylic position of the C-reagent to form the C-radical, which is oxidized to the carbocation; in turn, the aldehyde is oxidized to acid, which reacts with the carbocation to give the target coupling product 142 (Scheme 28). It was shown that under the reaction conditions, tert

Redox active dendronized polystyrenes equipped with peripheral triarylamines

• Toshiki Nokami,
• Naoki Musya,
• Tatsuya Morofuji,
• Keiji Takeda,
• Masahiro Takumi,
• Akihiro Shimizu and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2014, 10, 3097–3103, doi:10.3762/bjoc.10.326

• polystyrene equipped with peripheral triarylamines, which exhibited two sets of reversible redox peaks in the cyclic voltammetry curves. Keywords: carbocation; cross-coupling; dendrimer; dendronized polymer; redox; Introduction Assembling small functional molecules using dendrimers [1] and dendronized

• dendronized polystyrenes: (a) the functionalization of dendronized polystyrene (the “graft from” approach, Figure 1a); and (b) dendronization of polystyrenes with the dendritic carbocation equipped with functional groups (the “graft to” approach, Figure 1b). Both approaches have advantages and disadvantages

• than the oxidation potential of dendrimer 4, indicating that the triarylamine moiety is oxidized before the benzylsilane moiety. Using the “graft to” approach to synthesize peripherally functionalized dendronized polystyrene (Figure 1b) employing 5 as a precursor of the dendritic carbocation was

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• episelenonium ion 8 (Scheme 3). The episelenonium ion 8 should equilibrate with the ring-opened form, a benzylic type carbocation; the interaction of this intermediate with the opposing ethynyl substituent provides adduct 9. For steric reasons the chlorine anion attack from "outside" leading to intermediate 10

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• generated carbocation can proceed either by a Hofmann or a Saytseff mode, and – as the results show – both pathways are followed. Stereoelectronic reasons are presumably responsible for the slight preference of the Hofmann route. Not only does the methyl group appear to be sterically preferred for proton

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• the modified residues, most likely on the level of the iodinated phosphite intermediate [35], leading to the formation of an allylic carbocation in the bcen-T unit and 5’-phosphorylated DNA fragment (Scheme 3). The synthesis of oligonucleotides using building block 10 proved to be even more difficult

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• the R group has the ability to stabilize the carbocation, the electronic factor would favor the formation of the branched product (path b). The phosphorus atom has a stronger trans effect comparing with the oxazoline nitrogen, indicating that the carbon trans to phosphorus atom bears more