Electrophiles superelectrophilic activation

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... 

The concept of superelectrophilic activation was first proposed 30 years ago.20 Since these early publications from the Olah group, superelectrophilic activation has been recognized in many organic, inorganic, and biochemical reactions.22 Due to the unusual reactivities observed of superelectrophiles, they have been exploited in varied synthetic reactions and in mechanistic studies. Superelectrophiles have also been the subject of numerous theoretical investigations and some have been directly observed by physical methods (spectroscopic, gas-phase methods, etc.). The results of kinetic studies also support the role of superelectrophilic activation. Because of the importance of electrophilic chemistry in general and super-acidic catalysis in particular, there continues to be substantial interest in the chemistry of these reactive species. It is thus timely to review their chemistry. 

Superelectrophilic activation has also been proposed to be involved, based upon the reactivity of carbocations with molecular hydrogen (a a-donor).16 This chemistry is probably even involved in an enzymatic system that converts CO2 to methane. It was found that A. A -menthyl tetrahy-dromethanopterin (11) undergoes an enzyme-catalyzed reaction with H2 by hydride transfer to the pro-R position and releases a proton to give the reduced product 12 (eq 15). Despite the low nucleophilicity of H2, cations like the tert-butyl cation (13) are sufficiently electrophilic to react with H2 via 2 electron-3 center bond interaction (eq 16). However, due to stabilization (and thus delocalization) by adjacent nitrogen atoms, cations like the guanidinium ion system (14) do not react with H2 (eq 17). 

As noted previously in Chapter 1, the electrophilic reactivities of acetyl salts increase dramatically as the acidity of the reaction medium increases. This was one of the observations that lead Olah and co-workers to first propose the concept of superelectrophilic activation, or protosolvation of the acetyl cation, in 1975.2 This seminal paper described the chemistry of acetyl hexafluoroantimonate (CHsCO+SbFg-) and the reaction with alkanes in various solvents. In aprotic solvents such as SO2, SO2CIF, AsF3, and CH2CI2, there was no reaction. However in HF-BF3, acetyl salts react with Ao-alkanes and efficient hydride abstraction is observed.27 This was interpreted by Olah as evidence for protonation of the acetyl... 

The observed electrophilic reactivity is indicative of superelectrophilic activation in the dication 173. Other ammonium-carboxonium dications have also been reported in the literature, some of which have been shown to react with benzene or other weak nucleophiles (Table 4).1 42b 57-60 Besides ammonium-carboxonium dications (175-179), a variety of N-heteroaromatic systems (180-185) have been reported. Several of the dicationic species have been directly observed by low-temperature NMR, including 176, 178-180, 183, and 185. Both acidic (175, 180-185) and non-acidic carboxonium (176-177) dicationic systems have been shown to possess superelectrophilic reactivity. The quinonemethide-type dication (178) arises from the important biomolecule adrenaline upon reaction in superacid (entry 4). The failure of dication 178 to react with aromatic compounds (like benzene) suggests only a modest amount of superelectrophilic activation. An interesting study was done with aminobutyric acid... 

Superelectrophilic Activation or Superelectrophilic Solvation. Trifluoromethanesulfonic acid (triflic acid, TfOH) has been extensively employed as a superacid Ho= —14.1) in superelectrophilic activation (or superelectrophilic solvation), both concepts advanced by Olah. Superelectrophilic activations may occur when a cationic electrophile reacts with a Bronsted or Lewis acid to give a dicationic (doubly electron-deficient) superelectrophile. However, it should be recognized that the activation may proceed through superelectrophilic solvation without necessarily forming limiting dicationic intermediates. The frequently used depiction of protosolvated species as their limiting dications is just for simplicity. ... 

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. 

It should be recognized that superelectrophilic reactions can also proceed with only electrophilic assistance (solvation, association) by the superacids without forming distinct depositive intermediates. Pro-tosolvolytic activation of electrophiles should always be considered in this context. 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Nucleophilic reactions take place in the homocyclic ring, SwAr or AEc when it is activated by electron-withdrawing substituents. It has been described that halides can be displaced by a great number of nucleophiles via a normal and cine substitution [54,55]. Nitro containing Bfx has represented a class of neutral lO-TT-electron-defident system which exhibit an extremely high electrophilic character in many covalent nucleophihc addition and substitution processes. 4,6-Dinitrobenzofuroxan and others 4-nitro-6-substitutedbenzofuroxans (Scheme 2) have been defined as superelectrophiles and used as convenient probes to assess to the C-basicity of... 

MeZrCp2Cl, by virtue of the presence of the dipolar Cl+-AI bond. Most likely, this reaction exemplifies a widely observable principle of activation of an electrophile by another electrophile to generate a superelectrophilic species that has been termed the two-is-better-than-one principle.13 1... 

In summary, we have shown that stable cationic charge centers can significantly enhance the reactivities of adjacent electrophilic centers. Most of the studied systems involve reactive dicationic electrophiles. A number of the reactive dications have been directly observed by low temperature NMR. Along with their clear structural similarities to superelectrophiles, these dicationic systems are likewise capable of reacting with very weak nucleophiles. Utilization of these reactive intermediates has led to the development of several new synthetic methodologies, while studies of their reactivities have revealed interesting structure-activity relationships. Based on the results from our work and that of others, it seems likely that similar modes of activation will be discovered in biochemical systems (perhaps in biocatalytic roles) in the years to come. 

The key of alkane transformation was assigned to the formation of CX3+-type cations that are electrophilic enough (probably due to a second complexation of A1X3), to abstract a hydride anion from linear and cycloalkanes. When these cations are generated in superacidic media, a protosolvation induces a superelectrophilic character, which was supported by Olah on the basis of high-level ab initio calculations 65 The generation of these cations was also used by various teams66,67 to initiate selective low temperature alkane activation. 

Carboxylation of aromatics with carbon dioxide with AI2CI,/AI has been studied by Olah, Prakash, and co-workers425 and shown to be a chemoselective process to give aromatic carboxylic acids in good to excellent yields (20-80°C, CO pressure = 57 atm). Two possible mechanistic pathways with the involment of organoaluminium intermediates and complexes of C02 with AICI3 were postulated. On the basis of extensive experimental studies and theoretical calculations, the authors concluded that the most feasible mechanism involves CO2 activated with superelectrophilic aluminum chloride. Complex 116 reacts with aromatics in a typical electrophilic substitution. 

These results can be interpreted in terms of protosolvation of the nitronium ion. While the monocationic nitronium ion is a sufficiently polarizible electrophile to react with strong nucleophiles such as olefins and activated arenes, it is generally not reactive enough to react with weak nucleophiles including methane. Partial or complete protonation of the nitronium oxygen then leads to the superelectrophilic species 8. The... 

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). 

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). 

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