Carboxonium electrophiles

We have found several examples in which adjacent cationic charge centers are shown to activate carboxonium electrophiles. A convenient method for studying this activation is through the use of the hydroxyalkylation reaction, a commercially important, acid-catalyzed condensation of aldehydes and ketones with arenes.10 It is used for example in the synthesis of bis-phenol A from acetone and phenol (eq 6). While protonated acetone is able to react with activated arenes like phenol, it is not capable of reacting with less nucleophilic... 

The activating effects of ammonium groups on carboxonium electrophiles has also been exploited in the Friedel-Crafts acylations with amides.50 For example, in comparing the superacid-catalyzed reactions of acetanilide, the monoprotonated species (198) is found to be unreac-tive towards benzene (eq 67), while the diprotonated, superelectrophilic species (199) reacts with benzene to give the acyl transfer product in reasonably good yield (eq 68). 

In contrast, a persistent carbocation could not be generated from 9,10-dihydro-BaP introduction of bulky substituents at C-6 prevented side reactions, and the initially formed carbocation underwent rearrangement to the corresponding bay-region carbocation. Introduction of methoxy substituents into the 1- or 3- positions of 9,10-dihydro-BaP-7(8//)-one increased its electrophilic reactivity to the extent that stable carboxonium-arenium dications were produced in FSO3H/SO2CIF (Fig. 9). 

Alkylated carboxonium ions have also been prepared by direct electrophilic oxygenations of alkanes, alcohols, and so on, by ozone or hydrogen peroxide in superacidic media606 [Eq. (3.82)]. 

The electron withdrawing inductive effects of the fluorine substituents render the carboxonium ion 3 more electrophilic than carboxonium ion 2, and consequently it reacts with benzene. Thus, the electrophilic reactivity of the carbonyl group can be greatly enhanced by Brpnsted or Lewis acid solvation and by substitution with electron withdrawing groups. 

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... 

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... 

The inductive effects of the trifluoromethyl and trichloromethyl groups increase the electrophilic reactivities of the carboxonium ions when compared with those formed from acetophenone or acetaldehyde. 

Carboxonium ions are indicated to be involved in a number of super-electrophilic reactions. In several cases, the direct observation of the superelectrophiles and reactive dications has been possible using low... 

Carboxonium ions are an important group of electrophiles in chemistry.22 Carboxonium ions are categorized by the number of oxygen atoms bound to the carbon atom (one, two, or three) and by the groups bonded to the oxygen atoms (as acidic or non-acidic carboxonium ions). All of these types of carboxonium ions have the potential to form vicinal -dications by protonation or complexation of the non-bonded electron pairs of oxygen with acids (eq 40). 

The carboxonium-vinylic dication (68) is considered the key intermediate leading to the cyclization product. The analogous vinylic dications (69-71) have also been generated in superacid.31 Each of the species exhibits high electrophilic reactivity. 

Following electrophilic attack on benzene, the carbenium-carboxonium dication 94 is generated, which then gives the product 95. There have been several studies of the chemistry of malonic acid (80) and its esters in superacidic media. It has been shown that diprotonated products (i.e., 81) are formed (Table 1, entry 5).36... 

Carboxonium-Ammonium and Related Dications A wide variety of species have been generated in which the 1,3-dicationic structure arises from carboxonium ion centers being adjacent (separated by one carbon) to an ammonium or related charge center. These intermediates may be described as reactive dications, yet they have been shown to exhibit electrophilic reactivities comparable to superelectrophiles. 

Several types of nitrogen-containing heteroaromatic compounds are also capable of producing carboxonium-centered dications (Table 3).45 Among the dications 108-113, all have been shown to react with weak nucleophiles such as benzene, deactivated arenes, and even saturated hydrocarbons. Moreover, their reactivities greatly exceed that of comparable monocationic electrophiles. In the case of dication 111, for example, it is shown that it will condense with benzene in a hydroxyalkylative conversion (eq 36).45d... 

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). 

Initial ionization gives an ammonium-carboxonium dication, which then produces the ammonium-carbenium dication (230). A variety of dicationic electrophiles like 230 have been proposed. 

Among other distonic superelectrophiles described in the literature, there are carbo-onium dications. These include carbo-carboxonium dications, carbo-ammonium dications, and related ions. Despite the separation of charge in these superelectrophiles, some have been shown to have very high electrophilic reactivities. I. ike the carbodications described previously, the discussion here is limited to those systems that have been shown to have electrophilic reactivities greater than the related monocationic onium ions, as well as structural criteria supporting their designation as a distonic superelectrophilic species. 

Among the reported distonic superelectrophiles, a significant number of ammonium-carboxonium dications and related species have been studied. It has been shown that these electrophiles show enhanced reactivities compared with monocationic carboxonium ions. For example, 4-piperidone (172) is diprotonated in superacidic CF3SO3H to give the distonic superelectrophile (173), which condenses with benzene in high yield (eq 59).56 In contrast, cyclohexanone forms the monocationic carboxonium (174) ion, but ion 174 is not sufficiently electrophilic to react with benzene (eq 60). 

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... 

Aldehydes and ketones react with aromatic compounds in the presence of Bransted or Lewis acids. The actual electrophile is the carboxonium ion formed in an equilibrium reaction by protonation or complexation, respectively. The primary product is a substituted benzyl alcohol, which, however, is not stable and easily forms a benzyl cation. The latter continues to react further, either via an SN1 or an El reaction. Thereby, the following overall functionalizations are realized Ar—H —> Ar—C-Nu or Ar—H — Ar—C=C. 

Phenols are such good nucleophiles that protonated carbonyl compounds functionalize two phenol molecules. The first phenol molecule reacts in an Ar-SE reaction by the carboxonium ion formed in an equilibrium reaction. Subsequently, the second equivalent of phenol becomes the substrate of a Friedel-Crafts alkylation. The electrophile is the benzyl cation that is formed from the initially obtained benzyl alcohol and the acid. Protonated acetone is only a weak electrophile for electronic and steric reasons it contains two electron-donating and relatively large... 

The carboxonium ions of Figure 9.10 act as electrophiles in the polymerization of formaldehyde and formaldehyde hydrate. The most simple of them has the structural formula A, i.e., it is protonated formaldehyde from which the carboxonium ions B, C, E and so on are formed successively. The nucleophile causing these conversions is formaldehyde, which reacts with the cited electrophiles via its carbonyl oxygen and thus acts as a heteroatom nucleophile. 

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