Superelectrophiles substitution

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... 

Prakash, Olah, and co-workers256 have prepared Mosher s acid analogs by the hydroxyalkylation of substituted benzenes with ethyl trifluoropyruvate [Eq. (5.95)]. Deactivated aromatics (fluorobenzene, chlorobenzene) required the use of excess triflic acid indicative of superelectrophilic activation.3 5 In contrast to these observations, Shudo and co-workers257 reported the formation gem-diphenyl-substituted ketones in the alkylation of benzene with 1,2-dicarbonyl compounds [Eq. (5.96)]. In weak acidic medium (6% trifluoroacetic acid-94% triflic acid), practically no reaction takes place. With increasing acidity the reaction accelerates and complete conversion is achieved in pure triflic acid, indicating the involvement of diprotonated intermediates. 

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. 

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... 

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... 

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). 

This is reasonably close to the experimentally determined value of AFF = 11.1 kcal/mol for the superelectrophilic cyclization of 62 (eq 12). Another computational study showed that the energy barriers dramatically decrease for the electrocyclization when the monocations are protonated to form superelectrophiles. In the case of 63, cyclization provides the acetyl-substituted fluorene in 70% yield from CF3SO3H (Scheme 5). At the B3LYP/6-31 level of theory, dication 64 is estimated to have a cyclization barrier to fluorene of 8.5 kcal/mol, compared to a value of 25 kcal/mol for the cyclization of monocation 65. 

Similarly, kinetic experiments have shown that superelectrophilic carboxonium dications are involved in the cyclodehydrations of 1,3-diphenyl-l-propanones.4a Several examples of the cyclodehydrations were described, including the trifluoromethyl-substituted system (Scheme 14 ... 

Another class of gitonic superelectrophiles (based on the 1,3-carbodica-tion structure) are the Wheland intermediates or sigma complexes derived from electrophilic aromatic substitution of carbocationic systems (eq 8). 

Several gitonic superelectrophiles have been reported having closely oriented oxonium and carboxonium ion centers, some of which may be considered 1,3-dications. A series of hydroxy-substituted carboxylic acids were studied in FSOsH-SbFs in solution and the oxonium-carbonium dications could be directly observed at low temperature.57 In the case of lactic acid, dication 147 is a persistent ion at — 80°C, but at temperatures above — 60°C, formation of the diprotonated lactide (148) is observed (eq 48). 

The instability (and superelectrophilic nature) of aliphatic 1,4-dicationic systems can be seen in the failure to prepare some analogous cyclopropyl and 2,5-dimethyl-substituted 2,5-norbomadiyl dications (eqs 5 and 7).4... 

Water elimination in the superacidic solution is a highly exothermic step, but nevertheless the 2,6-adamantadiyl dication 34 is not formed. This observation suggests that structures like 34 can be distonic superelectrophiles. As in the case of other 1,4- and 1,5-carbodications, the 2,6-adamantadiyl dications are stabilized and persistent when the carbenium centers bear an aryl substituted (vide infra). 

There are a number of other aryl-substituted carbodicationic systems that can be properly described as distonic superelectrophiles. For example, dication 45 has been generated from 2,2 -p-phenylenedi-2-propanol in SbFs at —78°C.4 When compared to the dimethyl(phenyl)carbenium ion (cumyl cation) 46, NMR data indicate that the positive charges are dispersed to a considerable extent into the neighboring methyl groups in the dication 45. 

Other distonic superelectrophiles arise from aryl-substituted carbodicationic systems in which the positive charge centers are forced into close... 

Several reports have suggested that carbo-carboxonium superelectrophiles may also be produced from phenols, naphthols, and related species, by diprotonation in superacidic media.34 For example, 1-naphthol is thought to form the distonic superelectrophile (93) with a variety of acids (excess AICI3, HF-SbFs, and HUSY zeolite).343 In the presence of benzene, the substituted tetralone, and with cyclohexane, 1-tetralone is produced (eq 34). 

A number of related distonic superelectrophiles have been generated from A-heteroaromatic compounds (Table 2). Vinyl-dications (111-112) have been produced from the ethynyl pyridines,40 while /V-alkenyl A-heterocycles provide dications (113-115).42a Vinyl-substituted A-heterocycles provide access to distonic superelectrophiles such as dication 116.39 Dications 117 and 118 are generated from their precursors, and both intermediates lead to efficient cyclization reactions with the adjacent... 

A DFT study of the molecular orbitals of pyridine and a number of heteroaromatics unreactive to electrophilic substitution shows that the HOMOs of these compounds are not r-orbitals and so their low reactivity can be explained by assuming frontier orbital control of their substitution reactions.1 Consistent with this rationalization is the fact that in the case of pyridine-A-oxide and a number of other reactive substrates the HOMOs are n-orbitals. 4,6-Dinitrobenzofuroxan (1) is a superelectrophile and reacts with some supernucleophilic l,3,5-tris(A,A-dialkylamino)benzenes to form the first observed Meisenheimer-Wheland zwitterionic complexes [e.g. (2)].2... 

In contrast to NO, with superelectrophilic NOH and other hard electrophiles (H, I), (1 Ii, (. If . OH, F ), methane preferentially reacts similarly to its protonation to give CH5 or by hydride abstraction. These studies have reaffirmed the general pattern of electrophilic substitution of methane with strong electrophiles, which proceed via pentacoordinate carbocations involving 3c-2e C-H bonds, as previously suggested by Olah. 

Aromatic carboxylic acids were obtained in good to excellent yield by carboxylation of aromatics with a carbon dioxide-Al2Cl6/Al system at moderate temperatures (20-80°C).82 In a stoichiometric reaction, the dichloroaluminate salts of carboxylic acids were formed. Experimental results and DFT calculations suggested that the most probable pathway involved activation of C02 by the superelectrophilic aluminum chloride and its reaction with the aromatics in a typical electrophilic substitution. 

This study reports on the reactions of ambident nucleophiles with electron-deficient nitroaromatic and heteroaromatic substrates anionic complex formation or nucleophilic substitution result. Ambident behavior is observed in the case of phenoxide ion (O versus C attack) and aniline (N versus C attack). O or N attack is generally kinetically preferred, but C attack gives rise to stable thermodynamic control. Normal electrophiles such as 1,3,5-trinitrobenzene or picryl chloride are contrasted with superelectrophiles such as 4,6-dinitrobenzofuroxan or 4,6-dinitro-2-(2,4,6-trinitrophenyl)benzotriazole 1-oxide (PiDNBT), which give rise to exceptionally stable a complexes. Further interesting information was derived from the presence in PiDNBT of two electrophilic centers (C-7 and C-l ) susceptible to attack by the ambident nucleophilic reagent. The superelectrophiles are found to exhibit lesser selectivity toward different nucleophilic centers of ambident nucleophiles compared with normal electrophiles. 

---