Aromatics, 6-membered ring-closure

Dehydrogenation of alkylbenzene over the platinum component yields phenylalkenes. Protonation of the phenylalkene over the acid component forms a carbonium ion. (A phenylallyl cation may be produced by proton addition to phenylbutadiene or by hydride ion removal from a phenylalkene.) Attack of this carbonium ion on the aromatic ring closes either a five- or six-membered ring. Stabilization of the product occurs by proton elimination or hydride abstraction. This step may be followed by dehydrogenation to the thermodynamically most-stable species (e.g., to an alkylnaphthalene in the case of six-membered ring closure). (See p. 308.)... 

Scheme 29 6-membered ring-closure onto aromatics... 

Aromatic isonitriles, particularly orf/jo-alkenyl-substituted aryl isonitriles, were also successfully employed by Fukuyama in the synthesis of indole derivatives [19]. Cyclization of compounds 26 was accomplished with tin radicals, and 6-membered ring closure did not significantly compete except in one case (R = -Bu) where, on the other hand, this problem was interestingly alleviated by using the Z-alkene instead of the Z-analog (Scheme 11). 

The same methodology applies to heteroarylpentenes which lead to heterocyclic compounds fused with a cyclohexane (cyclopentane fused-heterocycles are not available since the five-membered ring closure onto the aromatic is too slow to compete with the oxidative elimination) (equation (64)) [128]. Even though the reactions are usually performed under thermal conditions in aqueous acetic acid at 90 °C, it has been shown to proceed faster under sonication, although in slightly lower yields. 

Additional experiments were carried out to examine the formation of toluene from n-heptane When the heptane was labeled with in the 1-position, half the radioactivity was in the methyl group and the other half was in the aromatic ring of the toluene. This clearly indicates that ring formation involves 1,6 or 2,7 closure and excludes the possibility of any interconversion between five membered and six membered rings. Perhaps this is not surprising since the catalyst s acid sites are neutralized by the sodium. 

The mechanism of this novel process is proposed to involve formation of a nine-membered ring, which after tautomerization undergoes an electrocylic ring closure to form the bicyclo[4.3.0]nonadienone intermediate. Elimination of ROH gives the aromatic product observed (Scheme 79). 

The primary product of the Heck type ring closure is an indole derivative containing an exocyclic double bond. This compound, however in most cases isomerises spontaneously to the aromatic isomer. In the example shown in 3.9. the addition of silver carbonate prevented the isomerisation of the double bond into the five membered ring.12... 

One of the rare examples, where the palladium catalyzed closure of a six membered ring leads to an aromatic heterocycle is presented in 4.18. Intramolecular transformation of the 2-bromoindole derivative in the presence of a palladium-BINAP catalyst led to the formation of the a-carboline (pyrido[2,3- ]indole) skeleton. The ring closure was accompanied by the oxidation of the intermediate dihydrocarboline derivative.21... 

Polyfluorinated a-diketones react with 1,2-diamino compounds, such as ort/io-phenylenediamine, to give 2,3-substituted quinoxalmes [103] Furthermore, the carboxyl function of trifluoropyruvates offers an additional electrophilic center. Cyclic products are obtained with binucleophiles [ 13, 104] With aliphatic or aromatic 1,2-diamines, six-membered heterocycles are formed Anilines and phenols undergo C-alkylation with trifluoropyruvates in the ortho position followed by ring closure to form y-lactams and y-lactones [11, 13, 52, 53, 54] (equation 23). 

Concurrently with the discovery and development in this country of the catalytic conversion of paraffins to aromatics (131) three different groups in the U.S.S.R. discovered this reaction independently of each other. Moldavskil and co-workers (238,239) showed that paraffins with six or more carbon atoms form aromatics by closure of a six-membered ring. For example, n-octane gives xylene and some ethylbenzene over amorphous chromia at about 470°C. Olefins also undergo this reaction. In subsequent publications, the group headed by Moldavskil demonstrated that molybdenum sulfide, titanium dioxide, and other oxides as well as activated carbon also may be used for dehydrocyclization (237,239). 

Distinct functional groups with acidic hydrogens can also promote these transformations. For instance, benzoylnitromethane (208) or ethyl bromopyruvate (206) react with isoquinoline (6) and acetylenedicarboxylates via the same dipolar mechanism to generate a pyrrolo[2,l-a]isoquinoline scaffold. However, in these cases, after closure of the 5-membered ring, a double-bond formation via dehydrogenation or nitrous acid elimination yields the fully aromatic ring systems 207 and 209 (Scheme 28) [82, 183]. 

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