Superacids dicationic species

Various other heteroatom-substituted earbocations were also found to be activated by superacids. a-Nitro and a-cyanocarbenium ions, R2C N02 or R2C CN, for example, undergo O- or N-protonation, respectively, to dicationic species, decreasing neighboring nitrogen participation, which greatly enhances the electrophilicity of their carbo-... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Olah generated similar dicationic species upon treatment of 4-hydroxy- or 4-methoxy- nitrosobenzenes with 1 1 HSO F-SbFs in SO2 (Scheme 6) These species were stable in the superacid media and were characterized by NMR spectroscopy. No nitrenium ion species were detected. Although Olah was unable to detect simple monoarylnitrenium ions, a few stabilized diarylnitrenium ions were detected during cyclic voltammetry experiments on the corresponding diarylamine in CHsCN, For example, the di-para-anisylnitrenium ion and its conjugate acid (Scheme 7) were both observed. This ion had a lifetime of about 1 s in CH CN. ... 

Superacid dehydrative cyclization of pinacols such as (93) gives condensed aromatic compounds as shown, presumably via dicationic species like (94).137... 

Protonated phenols and phenol ethers formed in superacids can be trapped by aromatics (benzene, naphthalene, tetrahydroquinoline). The products are either cyclohexenone derivatives301 [Eq. (5.112)] or aryl-substituted phenols. In the reaction of phloroglucinol with benzene, the diphenyl-substituted derivative is the main product [Eq. (5.113)], whereas 1,3,5-trimethoxybenzene gives selectively the monophenyl derivative (80% yield). Protonated dicationic species, such as 76, detected by Olah and Mo302 using NMR, were suggested to be intermediates in these processes. 

Superacid-promoted dicationic species containing heteroaromatic rings, where positive charge centres migrate through consecutive deprotonation-reprotonation steps, undergo cyclization reactions followed by aromatization and superacid-promoted elimination of benzene (Scheme 10).31 The process leads to the synthesis of aza-polycyclic aromatic compounds in moderate to good yields. Seven examples include pirazole, oxazole, and thiazole heterocycles. 

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). 

The dicationic species have also been obtained from /3-ketoacids, fi-ketoesters, and /-i-ketoamides in superacid solutions (Table 1, entries 2-4). Diprotonated acetoacetic acid (75) can be observed by low-temperature NMR under stable ion conditions.34 Likewise, diprotonated methylacetoacetate (77) can be observed by NMR at temperatures lower than — 80°C in FS03H-SbF5-SC>2 solution.35 With ethyl acetoac-etate in HF-SbFs, the equilibrium constant for the dication-monocation equilibrium has been estimated to be at least 107, indicating virtually complete conversion to the superelectrophile.35 The /3-ketoamide (78) is found to give the condensation products 95 in good yield from CF3SO3H and the superelectrophile 79 is proposed as the key intermediate in the condensation reaction (eq 25 ).27... 

Another novel class of oxonium dications involves the superacid-promoted ring opening reactions of oxazolines and related conversions.61 Oxazolines are well known for their ability to react with strong nucleophiles (i.e. alcohols) when protonated at the ring nitrogen 62 It was shown that the dicationic species (161 or 162) are capable of reacting with weak nucleophiles such as benzene (eq 52). 

C NMR spectroscopy shows the C2 resonance at < 13C 165.1 and Cl resonance at 128.3. As expected with the formation of dication 210, (Z)-/3-nitrostyrene 211 gives the identical spectra from CF3SO3H. Cryoscopic experiments also confirmed the formation of the dicationic species in the superacid. 

An analogous series of dicationic species have been proposed in the reactions of nitro-substituted arenes in superacid. For example, 2-nitro-naphthalene (212) reacts in superacid to give the arylated product (214) in good yield (eq 62).74... 

Carbo-acyl dicationic species have been proposed as intermediates in several reports, but these types of distonic superelectrophiles have not yet been sufficiently studied. Work by the Olah group has shown that pro-tonated carboxylic acids cleave to the acyl ions in superacidic media at temperatures above — 10°C.32 In principle, ionization of a second group (such as hydroxyl or olefinic) can generate a carbocationic site adjacent to... 

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... 

There have been several distonic superelectrophiles described in the literature that are oxonium-centered dications. For example, a series of diols were solvated in FSOsH-SbFs-SC and the dicationic species were persistent at —80°C.77 Upon warming to 25°C, the bis-oxonium ions undergo rearrangement to the more stable carboxonium monocations (eq 77). Barring a concerted mechanism, the transformations are thought to involve the carbo-oxonium dications (i.e., 225) and concomitant hydride shifts. Interestingly, 2,5-hexanediol ionizes in superacid, and with warming the cyclic oxonium ion (229) is formed (eq 78). 

In the last two decades many useful reactions and synthetic approaches involve superelectrophihc activation of reagents mediated by hquid superacids or by excess of aluminium halides. As an example, 0 ,j3-unsaturated aldehydes, ketones, acids or amides, readily condense with aromatics such as benzene and dichlorobenzene which are poor nucleophiles, but only in the presence of a large excess of aluminium chloride or triflic acid. This reactivity has been interpreted by the intermediacy of dicationic species. 

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). 

Evidence for the involvement of the diprotonated species 40 and 42 includes 13C NMR data, which shows deshielding of the involved carbons as the acidity of the media increases from H0 —8 to —26 (mesityl oxide is estimated to be fully monoprotonated in acids of about H0 —8). Dication 42 has been shown to be capable of reacting even with very weak nucleophiles, for example, abstracting hydride from cyclohexane.19b An analogous species (43) has been proposed in interaction with excess AICI3. Protonated cyclohex-2-enone is converted to 3-methylcyclo-pent-2-enone in HF-SbFs solution at 50°C.20 The reaction mechanism is thought to involve the dicationic intermediate 44 (eq 13). Likewise, aryl-substituted indenones are converted to the dications by reaction in superacid (eq 14).21... 

A series of phosphonium-carboxonium dications have also been studied in superacid catalyzed reactions.313 When the dicationic electrophiles are compared with similar monocationic species, it is clear that the phos-phonium group enhances the electrophilic character of the carboxonium center. For example, protonated acetone is incapable of reacting with benzene in condensation reactions, however, the phosphonium-substituted carboxonium ion (124) reacts in high yield (eq 40). 

There have been several types of gitonic superelectrophiles having acyl cationic groups as part of a 1,3-dicationic system. Monocationic acyl cations (168) can be prepared as persistent species in superacidic media and salts have even been studied by X-ray crystallography.113 Much of the interest in superelectrophilic species from acyl cations has focused on the protioacyl dications (169, vide supra).61... 

Besides carbo-ammonium dicationic systems, there have been studies related to carbo-phosphonium dication systems. Some of the reported chemistry suggests that superelectrophilic activation is involved. Olefinic phosphonium salts are protonated in superacid to generate dications like 140 and these species have been shown to react with benzene in good... 

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