Superelectrophiles examples

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

Similar to oxonium ions, our studies of sulfonium ions also showed protosolvolytic activation in superacids to give sulfur superelectrophiles. The parent sulfonium ion (HjS ), for example, gives H4S (diprotonated hydrogen sulfide) in superacids. 

Various sulfonium and carbosulfonium ions show remarkably enhanced reactivity upon superelectrophilic activation, similar to their oxygen analogs so do selenonium and telluronium ions. The alkylating ability of their trialkyl salts, for example, is greatly increased by protosolvation. 

Examples of some superelectrophiles so far studied and their parents are... 

Zhang, Y. Briski, J. Zhang, Y. Rendy, R. Klumpp, D. A. Superacid-Catalyzed Reactions of Olefinic Pyrazines an Example of Anti-Markovnikov Addition Involving Superelectrophiles. Org. Lett. 2005, 7, 2505-2508. 

Formylation of isobutane with carbon monoxide in the presence of an excess of A1C13 was first reported by Nenitzescu to yield, among others, methyl isopropyl ketone (31%).168 A new highly efficient superelectrophilic formylation-rearrange-ment of isoalkanes by Olah and coworkers has been described.282 Selective formation of branched ketone in high yield with no detectable branched acids, that is, the Koch products, was achieved. A particularly suitable acid is HF—BF3, which transforms, for example, isobutane to methyl isopropyl ketone in 91% yield. The... 

Since the inception ofthe superelectrophilic concept in the 1970s1 and 1980s 2 first formulated as protosolvation of cationic intermediates, superelectrophiles as highly reactive dicationic and tricationic intermediates have been successfully observed and characterized.3-5 Consequently, selected examples of superelectrophiles are also covered in this chapter where appropriate, whereas various organic transformations, in which the involvement of superelectrophilic intermediates is invoked or superelectrophiles are observed, are treated in Chapter 5. 

As already mentioned and shown, considerable experimental and theoretical evidence has been collected over the last decades, which supports the idea of superelectrophilic activation, that is, protosolvation1 2 or de facto protonation of cationic intermediates.3-5 Examples of superelectrophiles as highly reactive dica-tionic (doubly electron-deficient) and tricationic intermediates were discussed in Chapter 4. 

The success of carbocation chemistry lies in the stabilization of carbocations in a medium of low nucleophilicity. Superelectrophiles, in turn, are reactive intermediates generated by further protonation (protosolvation). This second protonation increases electron deficiency, induces destabilization, and, consequently, results in a profound increase in reactivity. In particular, charge-charge repulsive interactions6 play a crucial role in the enhanced reactivity of dicationic and tricationic superelectrophilic intermediates. As various examples of acidity dependence studies show, without an appropriate acidity level, transformations may occur at much lower rate or even do not take place at all. In addition to numerous examples of superacid catalyzed reactions, various organic transformations, in which the involvement of superelectrophilic intermediates is invoked or superelectrophiles are de facto observed in the condensed state, are also included in this chapter. 

Aminothiazole and its 4-methyl derivative react with the superelectrophilic 4,6-dinitrobenzofuroxan at C(5) to form, for example, (1) in spite of them exhibiting higher nitrogen basicity than aniline.7 In the case of 4,5-dimethyl-2-aminothiazole, however, attack did occur at nitrogen. 

Two types of interactions have been shown to be involved in superelectrophilic species. Superelectrophiles can be formed by the further interaction of a conventional cationic electrophile with Brpnsted or Lewis acids (eq 16).23 Such is the case with the further protonation (protosolvation) or Lewis acid coordination of suitable substitutents at the electron deficient site, as for example in carboxonium cations. The other involves further protonation or complexation formation of a second proximal onium ion site, which results in superelectrophilic activation (eq 17).24... 

One of the defining features of superelectrophiles is the often-observed high level of reactivity towards nucleophiles of low strength.1 This experimental observation is frequently used as an indication for the involvement of a superelectrophiles. To illustrate, the following examples show how the electrophile s reactivity can be characterized to indicate superelectrophilic chemistry. 

Friedel-Crafts type reactions of strongly deactivated arenes have been the subject of several recent studies indicating involvement of superelectrophilic intermediates. Numerous electrophilic aromatic substitution reactions only work with activated or electron-rich arenes, such as phenols, alkylated arenes, or aryl ethers.5 Since these reactions involve weak electrophiles, aromatic compounds such as benzene, chlorobenzene, or nitrobenzene, either do not react, or give only low yields of products. For example, electrophilic alkylthioalkylation generally works well only with phenolic substrates.6 This can be understood by considering the resonance stabilization of the involved thioalkylcarbenium ion and the delocalization of the electrophilic center (eq 4). With the use of excess Fewis acid, however, the electrophilic reactivity of the alkylthiocarbenium ion can be... 

Although electrophilic reactions involving dications with deactivated arenes may suggest the formation of superelectrophilic intermediates, there are a number of well-known examples of monocationic electrophiles that are capable of reacting with benzene or with deactivated aromatic compounds. For example, 2,2,2-trifluoroacetophenone condenses with benzene in triflic acid (eq 12).13 A similar activation is likely involved in the H2SO4 catalyzed reaction of chloral (or its hydrate) with chlorobenzene giving DDT (eq 13). 

These examples illustrate how electrophilic systems can exhibit enhanced reaction rates and yields with increasing strength of the acidic reaction media. Both qualitative and quantitative kinetic studies strongly suggest the involvement of superelectrophilic species in reactions. 

In several recent studies, nitro-substituted olefins have been shown to exhibit high electrophilic reactivities in superacid-promoted reactions.29 NMR studies have been used to identify some of the superelectrophilic intermediates in these reactions. For example, it was found that nitroethy-lene reacts with benzene in the presence of 10 equivalents of CF3SO3H to give deoxybenzoin oxime in 96% yield (eq 29). Since the reaction does not occur with only one equivalent of TfOH, it was proposed that the N,N-dihydroxy-iminium-methylium dication (51) is generated. In spectroscopic studies, l-nitro-2-methyl-l-propene (52) was dissolved in CF3SO3H, and at —5°C the stable dication (53) could be directly observed by and 13 C NMR spectroscopy (eq 30). 

Mass spectrometric techniques also enable experimentalists to react dications and trications with neutral substrates in the gas phase to explore the chemical reactions of these multiply charged species. Although only a few superelectrophiles have thus far been examined experimentally for their gas phase chemical reactivities, other electrophilic gas phase reactions have demonstrated the potential of these methods. For example, the... 

Quantum mechanical calculations are an essential part of chemistry, and these methods have been extremely useful in studies of superelectrophilic chemistry. For example, computations have been used in some studies to show that the formation of dicationic superelectrophiles lowers... 

Computational methods have also been used frequently to estimate the thermodynamic stabilities of superelectrophiles. These calculations have often involved the estimation of barriers to gas phase dissociation or deprotonation, and the proton affinities of conventional electrophilic intermediates. Other useful studies have calculated the heats of reactions for isodesmic processes. An interesting example of these calculations comes from a study of the protoacetyl dication (Cf COH2"1- ).42 In calculations at the 6-31G //4-31G level of theoiy, the protoacetyl dication (83) is estimated to react with methane by hydride abstraction with a very favorable... 

In superacid catalyzed reactions of hydroxyquinolines and isoquinolines, dicationic superelectrophiles were proposed as intermediates in their reactions (see Table 4).35d In order to explain differences in relative reactivities between the isomeric superelectrophiles, the energies of the lowest unoccupied molecular orbitals Ultimo ), the square of the coefficients (c2) at the reactive carbon atoms, and the NBO charges (q) on CH groups were determined by MNDO and DFT computational methods. For example, 8-hydroxyquinoline (85) is found to be more reactive than 6-hydroxyquinoline (87) in the superacid catalyzed reactions with benzene and cyclohexane (eqs 47 -8). 

In most of the examples of superelectrophilic reactions involving Lewis acids, they are conducted using an excess of the Lewis acid. This is in accord with electrophilic solvation by the Lewis acid, i.e. activation of the electrophile requires interaction with two or more equivalents of Lewis acid. As an example, superelectrophilic nitration can be accomplished with NO2CI and at least three equivalents of AICI3 (eq 23).46 This powerful nitrating reagent involves a superelectrophilic complexed nitronium ion (33). 

In addition to the discussed Br0nsted or Lewis superacidic activation in solution chemistry, there have been reports to suggest that superelec-trophilic species can be formed with solid acids, and even in biochemical systems. For example, Sommer and co-workers have found several examples in which HUSY zeolite has exhibited catalytic activity similar to liquid superacids (eqs 33-34).12 In the same study, the perfluorinated resinsulfonic acid Nafion-H (SAC-13) was found to give products consistent with the formation of the superelectrophile (36, eq 35). 

Lower temperatures were also an important aspect of other studies of superelectrophilic chemistry. For example, Olah and co-workers studied the role of superelectrophiles in the acid-catalyzed cleavage of esters.34 One of the key experiments was carried out under highly acidic conditions and at —40°C to prevent nucleophilic attack of monocationic intermediates (eq 44). 

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