Oxepines types

From the fruits extracts of L. nobilis, costunolide, santamarm, reynosin, gazaniolide, 11,13-dehydrosantonin and spirafolide were isolated as known sesqniter-pene lactones (Fig. 6.7). The dichloromethane fraction also afforded a new sesquiterpene, named lauroxepine, which had oxepine type sesqniterpene stractnie as an derivative of spirafolide [20]. However, its activity was the least (IC = 34.6... 

A precedent<42) for this type of reaction can be found in the formation of benz[/]oxepin (42) from the epoxide (41) ... 

An example illustrating the synthesis of condensed oxepins by the cobalt-catalyzed reaction of bistrimethylsilylacetylene with a hexa-l,5-diyne derivative is shown in Scheme 175.234 This type of process has been discussed earlier in the context of pyran synthesis (see Scheme 158 in Section V,B,2). 

Scheme 15. Carbohydrate-type oxepine via cyclopropanation of a glycal.

Of the three types of oxepines shown in Fig. 7, those of the enol ether type (136) seem to be the most versatile in terms of their ability to form septanose glycosides. 

A further type of photoisomerization mechanism for oxepin (7) was found by using material specifically labelled with 2H at the 3- and 6-positions (74JA5578). The location of the 2H atoms in the finally isolated sample of (7) was consistent with the migration of the oxirane ring to a neighboring position. The latter process (Scheme 13) has been described... 

The NIH shift has been found to occur during aromatic hydroxylations catalyzed by enzymes present in plants, animals, fungi and bacteria. It is thus evident that the acid catalyzed (or spontaneous) isomerization of oxepins-arene oxides is a very important type of in vivo reaction. It should be emphasized that the NIH shift may occur under either acid-catalyzed or neutral (spontaneous) conditions (76ACR378). The direct chemical oxidation of aromatic rings has also yielded both phenols (obtained via the NIH shift) and arene oxides (80JCS(P1)1693>. 

While both hydrogenation and epoxidation reactions of (7) (and substituted forms) occur on the oxepin valence tautomer, cycloaddition reactions proceed more readily on the arene oxide form (where the diene is closer to planarity). Thus the dienophiles DM AD and maleic anhydride (MA) readily yielded [4 + 2] cycloadducts with (7) as shown in Scheme 22 (67AG(E)385). A similar type of singlet oxygen cycloaddition reaction gave an unstable endoperoxide (106) which upon heating yielded trans-benzene trioxide quantitatively (equation 14). (75JOC3743). 

The heterepine-heteronorcaradiene equilibrium exemplifed for oxepin in Scheme 2 represents perhaps the best known type of valence tautomerism met in seven-membered and larger heterocyclics. 

The related oxobicycle (210), on photolysis in carbon tetrachloride, is converted into the isomer (211) in high yield by an intramolecular cycloaddition.186 The same transformation has been observed in norbornadiene, and other intramolecular cycloadditions are known [see, for example, Eq. (50)187]. An intermediate of this type has been postulated188 to account for the photorearrangement of 1,4-epoxy -1,4-dihydronaphthalene to benz[/]oxepin [Eq. (51)]. 

Compound 162 is colorless and in isooctane possesses a UV spectrum of the cyclohexa-1,3-diene type, with a maximum at 258 nm (e = 4900). The reference for the oxepin structure is 157, which has a broad band at 297 nm (e = 1800) in isooctane. When the solvent polarity is increased or the temperature is lowered, the equilibrium shifts clearly from the oxepin to the epoxide form.8... 

Considered in this section are two groups of oxepine reactions (1) addition and cycloaddition reactions peculiar to their conjugated carbon chain, and (2) those characteristic of vinyl ethers, particularly, beginning from an attack on ring oxygen. Both reaction types are discussed in detail in CHEC(1984) and CHEC-II(1996) therefore, only several important new examples are given here. 

Compounds of the benzene oxide and benzene imide types are tautomeric with, and generally exist predominantly as, the seven-membered oxepin and azepine rings (see Sections 2.5.5.2 and 3.5.2.2). For arene oxides and related derivatives see . 

The control of furan versus oxepin manifolds has been addressed recently. Vinyloxiranes of type (139) yielded oxepins (140) at lower temperatures, whereas higher temperatures gave dihydrofurans (141 Scheme 29), indicating that the Cope-type rearrangement of cis-divinyloxirane may be controll by precisely defining the temperature profile of the flash vacuum pyrolysis. 

The very general picture of the mechanism given in the introduction needs to be modified somewhat. It is fairly clear that allylsilanes react in the manner illustrated as (3) — (5), except that the acid catalyst is almost invariably a Lewis acid not a proton. Protic acid is apt to induce protodesilylation in competition with carbon-carbon bond formation, but Lewis acids are less likely to attack the carbon-carbon double bond. The intervention of a cationic intermediate (4) has not been proved for this type of reaction, but there is good circumstantial evidence that cations are involved by analogy with protodesilylation,7 from the occasional formation of oxepins, without loss of the silyl group,8 and from the stereochemistry of the reaction. 

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