Superelectrophilic intermediates

G. Prakash, G. K. S. Efficient Chemoselective Carboxylation of Aromatics to Arylcarboxylic Acids with Superelectrophilically Activated Carbon Dioxide-Al2CI6/Al System. J. Am. Chem. Soc. 2002, 124, 11379-11391. (d) Klumpp, D. A. Rendy, R. McElrea, A. Superacid Catalyzed Ring-opening Reactions Involving 2-Oxazolines and the Role of Superelectrophilic Intermediates. Tetrahedron Lett. 2004, 45, 7959-7961. 

Moreover, recently the application of zeolites in organic synthesis demonstrated their ability to achieve reactions necessitating usually superelectrophilic intermediates as in superacid media.144 These results cannot be rationalized on the basis of the acidic character alone and needs the understanding of confinement effects145 in which case the zeolite cage behaves like a nanosized reactor favoring the contact between reactant and specific acidic sites. The electrostatic effects may also be important. 

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. 

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. 

Extending the concept of superacids to varied superelectrophiles has emerged as a productive new field in recent years (G. A. Olah and D. A. Klumpp, Superelectrophiles and Their Chemistry, Wiley-Interscience, Hoboken, NJ, 2008). Highly reactive and activated protosolvated or multiply charged superelectrophilic intermediates are involved in varied chemical reactions, many of them of substantial practical significance. 

Superelectrophilic intermediates have been categorized into two distinct groups the distonic (distant) and the gitonic (close) superelectrophiles (Table l).22 Distonic superelectrophiles are defined as electrophiles in... 

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... 

Diprotonated, superelectrophilic intermediates were suggested to be involved in both conversions. Considering protonated aldehydes, benzal-dehyde gives a carboxonium ion that is significantly resonance stabilized and thus unreactive towards aromatic substrates such as o-dichlorobenzene or nitrobenzene. Pyridinecarboxaldehydes, however, show much higher electrophilic reactivities due to their ability to form via TV-protonation the superelectrophile (5, eq 8).10 A similar situation is seen in the hydroxyalkylation reactions of acetyl-substituted arenes. Acetophenone is fully protonated in excess triflic acid, but the resulting carboxonium ion (6) is... 

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). 

Superelectrophilic intermediates were also proposed in the cyclization reaction of Q -(methoxycarbonyl)diphenylmethanol (37) with superacid (eq 24).25 The yield of cyclized product is found to increase dramatically with increasing acidity of the reaction medium. The conversion is believed... 

It was reported that arylpinacols (48a) can undergo a superacid-catalyzed dehydrative cyclization to give the aryl-substituted phenan-threnes (eq 27).23 Superelectrophilic intermediates were proposed in the conversion. Tetraarylethylene dications have been studied by several methods and were observed directly by NMR as well as by UV-vis spectroscopy and X-ray crystallography.28 The low temperature oxidation of tetraaiylethylenes gives the dicationic species (50, eq 28). 

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). 

A comprehensive series of ionic hydrogenation reactions have been studied by Koltunov, Repinskaya, and co-workers, and superelectrophilic intermediates have been proposed.34 Some of these intermediates have been characterized by and 13C NMR (Table 4). Many of these dicationic intermediates have been shown to react with cyclohexane by hydride abstraction, indicating superelectrophilic character. 

As mentioned previously, superelectrophilic intermediates were proposed in the reaction of o -(methoxycarbonyl)diphenylmethanol (37)... 

Table 4. Superelectrophilic intermediates observed by ll and 13C NMR spectroscopy and capable of hydride abstraction from cyclohexane34...

Although the exact nature of the superelectrophilic intermediate is not known, it was suggested that protosolvation of one or both of the iminium... 

Superelectrophilic intermediates have further been proposed in the reactions of some esters. For example, a recent report describes the conversions of methyl benzoate to benzophenone products (70-93% yields) in reactions with superacid (eq 45 ).52... 

It was proposed that product 167 arises from coordination of the isoxazolidine (164) to AICI3 to generate the dicationic, superelectrophilic intermediate (165), which undergoes ring-opening to give product 167 by a Friedel-Crafts type reaction. 

It has been demonstrated that nitronic acids and a-carbonyl nitro-methanes can form superelectrophilic intermediates in strong acids and the resulting species are capable of reacting with benzene (eqs 65-67).23... 

Superelectrophilic intermediates are typically generated when a cationic electrophile is further protonated or coordinated by a Lewis acid to produce a dicationic species. 

In TfOH medium, vinylpyrazine undergoes anti-Markownikow addition involving superelectrophilic intermediates. Arylation of such an electrophile with benzene gave 2-phenylethylpyrazine in high yield (eq 42). ... 

Dicarboxylic acids can also form a variety of distonic superelectrophilic intermediates by TfOH-mediated protonation of the carboxylic acid group and ionization of adjacent functional groups. 

A cyclodehydration methodology has been developed, leading to the imidazole [2,l-fl]isoquinoline ring system (Scheme 16). The chemistry is thought to involve dicationic, superelectrophilic intermediates. For example, the ketone (65) provides the... 

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