Cyclizations, superelectrophilic

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. 

Superelectrophilic intermediates were also proposed in the cyclization reaction of Q -(methoxycarbonyl)diphenylmethanol (37) with superacid (eq 24).25 The yield of cyclized product is found to increase dramatically with increasing acidity of the reaction medium. The conversion is believed... 

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). 

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). 

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. 

The described superelectrophilic activation and fluorene-cyclization is thought to involve a lowered energy of the LUMO and concomitant delocalization of positive charge into the aryl ring(s).32b Calculations at the 4-31G//STO-3G level on a model system (Figure 2) have shown that the amount of positive charge in the phenyl ring increases upon formation of the dication (67) when compared to the monocation (66) and the benzyl cation (calculations are based on fully planar structures). It is well known... 

With the monocationic species, no fluorene cyclization is observed. However upon addition of CF3SO3H, the cyclization occurs almost quantitatively. This is consistent with formation of the protonated, dicationic intermediate (46) leading to the cyclization product (59). In this same study, it is noted that other stable monocationic 1,1-diarylethyl cations (i.e., the 1,1-diphenylethyl cation) do not readily form the fluorene ring system, indicating the importance of superelectrophilic activation. 

Kinetic evidence suggests the involvement of gitonic superelectrophiles also in superacid-promoted Houben-Hoesch reactions.44 As discussed previously, 4-phenylbutyronitrile (6) is found to cyclize at an appreciable rate only in solutions more acidic than Hq —10 (eq 28). 

There have been two reports involving gitonic superelectrophiles composed of carboxonium ions and vinylic carbocations in a 1,3-relationship. In the reaction of 3-phenylpropynoic acid (65) with benzene in superacid the novel carboxonium-vinyl dication 66 is generated, followed by reaction with benzene and then cyclization (eq 22).26a Likewise, the unsaturated amide (67) gives the cyclization product in high yields (70-97%) in very strong acids (polyphosphoric acid, CF3SO3H, Nation SAC-13, or HUSY eq 23).30... 

A fair number of carbo-ammonium dicationic species and related systems have been reported. These distonic superelectrophiles have been directly observed and shown to be useful in synthetic methodologies. For example, the acid-catalyzed Grewe-cyclization is a well-known reaction used in the preparation of morphine analogues.37 The conversion involves formation of the distonic superelectrophile (102) from an appropriate... 

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... 

Smooth aza-Nazarov cyclization to form dihydroisoindolones is observed with TfOH where CE3COOH is totally ineffectual. Eormation of dicationic superelectrophilic species is apparently important for overcoming the energy barrier of the cyclization in such cases. ... 

---