Superelectrophiles temperatures

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. 

Superelectrophilic dications 50 have been observed by Coustard,197 who used 1H and 13C NMR spectroscopy in triflic acid at low temperature (Scheme 5.25). They... 

Knorr cyclization of a range of iV-susbtituted butyramides in triflic acid yields 4-methyl-17/-quinolin-2-one derivatives704 [Eq. (5.257)]. Suggested intermediates of the transformation directly observed by low-temperature multinuclear NMR spectroscopy (HSO3F SbF5 S02C1E, 40°C) are distonic superelectrophiles formed by diprotonation of the two carbonyl oxygen atoms. 

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). 

While many superelectrophilic reactions are accomplished at ambient or somewhat elevated temperatures, a significant number of conversions are found to work better at lower temperatures. As some of these reactions employ gaseous reagents such as HF, BF3, and low molecular weight alkanes, the lower temperatures may be necessary to help to keep the reagents in the condensed phase. In other reactions, the lower temperatures are used to control the excessive reactivities of the superelectrophiles... 

Table 3. Superelectrophilic reactions requiring more elevated temperatures.

Several conversions based on superelectrophilic hydroxycarbenium ions (such as 45) were also carried out at lower temperatures, including the condensation reaction (eq 41) and electrocyclization (eq 42).8,13 A similar electrocyclization reaction with a benzilic acid methyl ester was also found to proceed in high yield at —40°C (eq 43).22... 

The reactivity of superelectrophile 46 precludes its direct observation by NMR, but as discussed in Chapter 2, stabilization of the carbenium ion center with para -methoxyphenyl groups allowed the dicationic species (5) to be observed at low temperature. 

As discussed previously, several types of reactive dications and superelectrophiles have been directly observed using NMR spectroscopy. These experiments have all used low temperatures (— 100°C to — 30°C) and superacidic conditions to generate the observable reactive dications and superelectrophiles. Some reactive dications and superelectrophiles are stable at low temperatures and can be directly observed by NMR, but at higher temperatures they readily cleave and decompose. The low temperatures also slow down proton exchange reactions and enable the ions to be observed as static species. 

Lower temperatures were also an important aspect of other studies of superelectrophilic chemistry. For example, Olah and co-workers studied the role of superelectrophiles in the acid-catalyzed cleavage of esters.34 One of the key experiments was carried out under highly acidic conditions and at —40°C to prevent nucleophilic attack of monocationic intermediates (eq 44). 

There have been many studies related to tetraaryl-1,2-ethylene dications, formally gitonic superelectrophiles, which show extensive charge delocalization into the aryl rings (Scheme 1). Low temperature 13C NMR studies have shown that the para carbons are deshielded, from < 13C... 

Several lines of evidence in the studies of Ohwada and Shudo support the involvement of these gitonic superelectrophiles. An analagous dicationic species (47) has been directly observed by 1H and 13C NMR at low temperature in both CFsSOsH-SbFs and CF3SO3H solutions. With dication 47, the NMR spectra show an equivalence of the aromatic rings suggesting a perpendicular relationship between the two cationic centers. The dications having the 4-methylphenyl substituents (61-62) have likewise been directly observed by NMR at low temperature, and upon warming the solutions, the expected cyclization products are formed (eqs 11-12). 

Diazenium dications may also be considered gitonic superelectrophiles, but only a limited number of them have been prepared and studied.97 In principle, diazenium dications could be prepared by double alkylation or protonation of various azo-compounds. To date, only monalkylation has been achieved with strong alkylating agents (eq 57)97a However, Olah et al. showed that diazenium dications can be produced by double protonation of azobenzenes in FSQ3H-SbF5 at low temperature.97b It has also been demonstrated that the diazenium dications are prepared from electrochemical and chemical oxidations (eqs 58-59).97c,d... 

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... 

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). 

Several types of onium dications have been studied in which a single acyl cationic center has been part of 1,3-dicationic superelectrophiles. For example, pyruvic acid has been studied in FSOsH-SbFs solution at low temperatures.34 Initially the diprotonated species is observed in equilibrium with some of the monocation (eq 55). 

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... 

These distonic superelectrophiles (145-147) have been characterized by low-temperature H NMR (and 13C NMR in the case of 147) from FSO3H-SbFs solution. Dication 146 was also studied by calorimetric studies to determine the heat of diprotonation of 2,5-hexanedione.48 It was found that the heat of diprotonation for the y-diketones (like 2,5-hexanedione) is about 5 kcal/mol less than expected, when compared to twice the heat of protonation of acetone or other monoketones. The destabilization of dication 146 by 5 kcal/mol can be the result of electrostatic effects, and it can be considered evidence for the superelectrophilic character of such dications. When 2,6-admantanedione is reacted in FSO3H—SbFj solution, the dication 148 is formed as a persistent species, observable by and 13C NMR.12 The carboxonium carbons of 148 are observed at Z I3C 247.7, while the mono-cationic species (149) has a carboxonium carbon at 513C 267.1. These 13C NMR data were interpreted as evidence for the increasing importance of the carboxonium-type resonance structure (148a) due to electrostatic repulsive effects. Some examples of aromatic diketones (i.e., diacetylbenzenes) have also been reported to produce bis-carboxonium dications in their protonation reactions in superacids.47... 

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... 

Similar distonic superelectrophiles have been described as products from the superacidic reactions of hydroxy ethers. Olah and Sommer prepared and observed (by low temperature NMR) both 1,4- and 1,5-dioxo-nium dications (231-234).79... 

There is evidence for formation of a zwitterionic Meisenheimer-Wheland complex between superelectrophilic and supernucleophilic reagents. Thus, NMR spectra in CD2CI2 show the formation of (12) from 4,6-dinitrobenzofuroxan and l,3,5-lris(/V,/V-dialkylamino)benzenes. At temperatures above — 30 °C the spectra show the presence of a dynamic process interconverting the three equivalent ring positions of the nucleophile.51... 

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