Oxepin/benzene oxide, valence isomerization

Oxepin and its derivatives have attracted attention for several reasons. Oxepin is closely related to cycloheptatriene and its aza analog azepine and it is a potential antiaromatic system with 871-elcctrons. Oxepin can undergo valence isomerization to benzene oxide, and the isomeric benzene oxide is the first step in the metabolic oxidation of aromatic compounds by the enzyme monooxygenase. 

Oxidation of the 2,2 -biphenyldiol (218, Scheme 56) by one molar equivalent of lead tetraacetate affords the oxepinobenzofuran 219. With two molar equivalents of lead tetraacetate the initial product is converted to the acetate 221, which on reductive acetylation, involving oxepin-benzene oxide isomerization, affords the dibenzofuran 222. Treatment of the oxepinobenzofuran 219 with ethanolic 2,4-dinitrophenylhydrazine yields the azo compound 220. On boiling with methanol in air, compound 219 is converted to the dibenzofuranone 223, again involving valence isomerization. Reductive acetylation then affords the dibenzofuran 224. ... 

A feature of 1//-azepine chemistry that intrigued early researchers (B-69MI51600, 71 AG(E)ll) was the possibility of azepine-benzeneimine (or azanorcaradiene) valence isomerism (67AG(E)402) akin to that in the oxepin-benzene oxide system. 

Three decades ago the preparation of oxepin represented a considerable synthetic challenge. The theoretical impetus for these efforts was the consideration that oxepin can be regarded as an analog of cyclooctatetraene in the same sense that furan is an analog of benzene. The possibility of such an electronic relationship was supported by molecular orbital calculations suggesting that oxepin might possess a certain amount of aromatic character, despite the fact that it appears to violate the [4n + 2] requirement for aromaticity. By analogy with the closely related cycloheptatriene/norcaradiene system, it was also postulated that oxepin represents a valence tautomer of benzene oxide. Other isomers of oxepin are 7-oxanorbornadiene and 3-oxaquadricyclane.1 Both have been shown to isomerize to oxepin and benzene oxide, respectively (see Section 1.1.2.1.). 

In connection with the chemistry of the reactive transient species, nitrene, the chemistry of azepines is well documented u. Also, the chemistry of oxepins has been widely developed due to the recent interest in the valence isomerization between benzene oxide and oxepin and in the metabolism of aromatic hydrocarbons 2). In sharp contrast to these two heteropins, the chemistry of thiepins still remains an unexplored field because of the pronounced thermal instability of the thiepin ring due to ready sulfur extrusion. Although several thiepin derivatives annelated with aromatic ring(s) have been synthesized, the parent thiepin has never been characterized even as a transient species3). 

For the benzene sulfide-thiepine system, the rate of valence isomerization is predicted to be much slower than that in the benzene oxide-oxepine system, as the enthalpy of activation for 10 —> 1 is 20.5 kcal mol 1 (7.03 kcal mol for benzene oxide-oxepine). 

While the isomerization of benzene oxides to oxepins occurs spontaneously at low temperature, the analogous mobile valence tautomerization of m-benzene dioxide 143 (Figure 10) to the 10-tt-heterocycle, 1,4-dioxocin, was only evident at temperatures > 50°The latter process is symmetry-allowed and is formally equivalent to a retro-Diels-Alder reaction. The mobile equilibrium at 60°C appeared... 

P(0)(0Me)2] gives the pyrans 65a-b and the diazepines 67a-b. Diazepines 67a-b are formed by spontaneous isomerization of the intermediate 2-(diazomethyl)-2//-pyrans 66a-b (87JOC3851). In contrast, the analogous reactions of 4-methyl-2,6-diphenylpyrylium tetrafluoroborate 63b with 64a-b give only 68a-b. The allylpalladium chloride-catalyzed decomposition of 65a-b and 68a-b in benzene solution gives 92-98% of oxepines 69a-b,d. Oxepines 69a-b,d react with triazolinedione 55 to form the Diels-Alder adducts 70a-b,d (83-89%), which are derived from the valence tautomeric benzene oxides. The corresponding reaction of 69c with 55 under otherwise identical conditions proceeds differently in that an isomer with structure 70 c (66%) is formed along with 70c (23%). 

Oxepins and their bicyclic valence tautomers, arene oxides are discussed in <95CHE(42)197>. Particularly noteworthy is the synthesis of a stable benzene oxide (63) which surprisingly shows little tendency to isomerize to the corresponding oxepin (64) in spite of the expectation that the fluorines would greatly destabilize the three-membered ring in the bicyclic structure (63) (Scheme 10) <90JA6715>. 

The reaction of oxepin (228 R = H) was complicated by the simultaneous photochemical reaction of benzene oxide, the valence isomer of oxepin.26 The results varied with solvent, temperature, and wavelength.269 The reaction proceeded with high selectivity to 2-oxa-bicyclo[3.2.0]hepta-3,6-diene (229 R = H) upon irradiation (A >310 nm) at room temperature. In most other cases the reaction was attended with the formation of phenol, probably from benzene oxide via Dewar benzene oxide, as this compound is known to isomerize photo-... 

The possibility of valence isomerization also affects the reactions of the oxepins [5]. For instance, cycloadditions involve the benzene oxide, as shown by the Diels-Alder reaction with activated al-kynes, and give the epoxybicyclo[2.2.2]octatriene 9 or, in the presence of singlet oxygen, afford the peroxide 10. The latter isomerizes thermally yielding the ra .s-benzene trioxide 11 ... 

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