Bridged oxepines

The oxidation of oxepins generally results in cleavage of the ring. An exception is the bridged oxepin derivative diethyl 3,6-hexanooxepin-4,5-dicarboxylate which is oxidized with potassium permanganate in the presence of potassium carbonate to give diethyl 8-hydroxy-9-oxo-10-oxabicyclo[6.3.2]trideca-l(ll),12-diene-12,13-dicarboxylate in 39% yield (mp 98 C).130... 

Substituted and benzo-annulated oxepins readily undergo addition of bromine across the nonaromatic double bond. Bromination of 3,6-bridged oxepins can occur in two different ways, either as a 1,2-addition164 or as formal 1,4-addition to the diene system of the corresponding benzene oxide to give products i.129 138-140 164... 

The reactivity of the unsaturated system of oxepin gives rise to a variety of cycloaddition reactions. A number of 3,6-bridged oxepins have been reacted with peracids to give 2,3-ep-oxyoxepins i,129 154.213.218 At higher temperature, the 2,3,6,7-diepoxy derivatives 2 are formed.164... 

Irradiation of 3,6-bridged oxepins with ester functions in the 4- and 5-positions gives tricyclic structures 3 in which the oxepin oxygen becomes part of an aldehyde function.248-250 When chiral esters are used, it has been shown that the irradiation in solid state proceeds with a high degree of diastereoselectivity.249,251,252... 

From the analysis of the coupling constants of olefinic protons in conjunction with the UV spectrum of 2,7-pentamethylene-bridged oxepin, it has been found that the oxepin is in equilibrium with its mirror image in a nonplanar boat form [see Fig. 1, Eq. (4)].8... 

A pair of reductive eliminations on chlorohydrin intermediates was used to achieve regioselective introduction of alkene functionality in a synthesis of (18), a precursor of the sesquiterpenoid pentalenene (Scheme 7). Key steps in Tochtermann s synthesis of [6]-paracyclophane derivative (21 Scheme 8) were bromination of the bridged oxepine (19) followed by reductive elimination of the resultant dibro-mooxirane (20). 

Sequential epoxidation of a /f,/f-hexano-bridged oxepin (65) leads to the interesting mono- and bis-epoxides (66) and (67), respectively (Scheme 11) <82CB1162>. The double bonds adjacent to the oxepin oxygen proved to be the preferred sites of attack in both cases. 

The full report on the synthesis of the hexano-bridged oxepin (140) has now appeared and further work has been reported on its oxidative cleavage to give cyclodecenes and cyclodecadienes, and on some addition reactions. The structure of the dehydration product of 2,6-di-t-butyl-4-phenyl-l-(p-tolyl)cyclohexa-2,5-diene-l,4-diol, previously postulated as a fully unsaturated oxepin, has now been confirmed by X-ray analysis. ... 

Reactions of Oxygen-containing Compounds. - Studies of the bridged oxepin... 

ElectrocycHc ring opening of the cyclobutene rings in adducts 422 and 424 produces the bridged oxepine products 423 and 425 in high yields (Scheme 89 2000CEJ3706). 

Thermolyses of 3-oxaquadricyclanes with different substituents at C1(C5) and C6(C7) such as carboxy and phenyl groups showed that the reaction generally gives oxepins with the carboxy functions in the 4- and 5-position.24 This is also true when the substituents in the 6- and 7-positions form a bridge of six carbon atoms, e.g. formation of 9.129131 The rearrangement of these 3-oxaquadricyclanes gives access to the [6]paracyclophane system. 

With an octamcthylcne chain it is possible to bridge the two carbon atoms adjacent to the oxygen. On heating, the expected oxepin 10 with methoxycarbonyl groups in the 4- and 5-position is formed in 95% yield.132... 

The bridged annulene 5,10-epoxy[10]annulene behaves as an aromatic 1 Ore-system rather than an oxepin and reacts with copper(II) nitrate in acetic anhydride to give a 1 1 mixture of 1-and 2-nitro-5,10-epoxy[10]annulene 2 and 3.154... 

A number of oxepin derivatives with alkano bridges across the 3- and 6-positions and across the central C-C double bond have been oxidized with ruthenium(VIII) oxide. Usually, all of the double bonds of the heterocycle are cleaved and a macrocycle 5 is formed that contains two 1,2-diketone functions.142,199... 

The deoxygenation reaction by means of transition-metal complexes has been extended to oxepins with a tetramethylene bridge across the C2-C3 bond to give products 5.133... 

Bromine can also undergo addition to the nonaromatic double bond of dibenz[ft,/]oxe-pin.160,161 Oxygen-bridged annulenes that incorporate an oxepin structure have been shown to undergo 1,4-addition of bromine at — 78°C.159... 

When the hydride ion of lithium alanate is used as nucleophile, cyclohexa-2,4-dien-l-ol is obtained as a labile addition product which eliminates water on standing to give benzene.12 The reaction of an oxepin derivative that possesses a hexamethylene bridge across C3-C6 with sodium methoxide gives an addition product 5 in which the seven-membered heterocyclic system is retained.213 214... 

The preference of 2,7-disubstituted oxepins for this tautomeric form at equilibrium may be rationalized in terms of a steric substituent effect. The eclipsing interactions of the 2,7-substituents in the arene oxide form will be diminished by isomerization to the oxepin. When the 2,7-substituents form part of an annelated ring system, e.g. (22)-(24), the tautomeric preference will be determined by the size of the methylene bridge (67AG(E)385). Thus when n = 5 the annelated oxepin (24) was present in approximately equal proportions with the arene oxide form. However with n =4. (23) tetralin 9,10-oxide was dominant. The... 

Oxepin is obtained by photolysis of the 2,3-oxide of bicyclo[2.2.0]-hexa-2,5-diene112 [Eq. (29)] this process is, in fact, the reverse of the bridging reaction. 

The mechanism of the atroposelective ring opening of a lactone-bridged biaryl, dinaphtho[2,l-t l, 2 -< ]oxepin-3(5//)-one, with a chiral oxazaborolidine-BH3 complex (Scheme 2) was studied using semi-empirical AMI calculations <2000JOC2517>. 

Treatment of 1,2-C-methylene carbohydrates, prepared by cyclopropanation of unsaturated sugars, with Lewis acids and trapping of the intermediate oxonium ion with a nucleophile is a convenient route to 2-substituted-2,3,6,7-tetrahydrooxepines <95TL683i>. Thus rearrangement of (55) with TMSOTf in acetonitrile in the presence of MeCN affords (56). The trapping nucleophile may be a substituent of the original carbohydrate, as demonstrated by the conversion of (57) into the bridged bicyclic oxepine (58). 

Bridging substituent groups also influence the preference for either the arene oxide or the oxepin valence bond tautomer. Thus, when n = 3, indan 8,9-oxide 7 exists exclusively as the oxide form. With n = 4, tetralin 9,10-oxide 8 is dominant over its oxepin form while similar amounts of the arene oxide and oxepin are present when n = 5 (9). 

A donor-acceptor substituted biscyclopropane is an intermediate in an elegant preparation of a -bridged hexano-oxepin, which is formed by an electrocyclic ringopening (equation 87) ... 

The spontaneous oxepin-benzene oxide isomerization proceeds as a thermally allowed, disrotatory process according to the Woodward-Hoffmann rules. Because of eclipsing interactions, 2,7-substituents destabilize the benzene oxide structure and favour oxepin formation. If the 2,7-positions are bridged, the size of the bridge influences the oxepin-benzene oxide equilibrium. This is shown by studies of the 2,7-methylene-bridged systems 7 and 8 If n = 3, only the indane oxide is present if n = 4, tetrahydronaphthalene oxide predominates in the equilibrium mixture if n = 5, oxepin and benzene oxide are present in a ratio of 1 1 [4]. 

The flexibility of this method is illustrated by the synthesis of oxygen-bridged [lOJannulene 16. This compound is obtained from the tetrabromodecahydronaphthalene epoxide 14 together with the benzo[b]oxepin by way of 9,10-epoxynaphthalene 15 [7] ... 

The (4n+2) r-electrocyclization of l//-azepines is analogous to the oxepin-benzene oxide rearrangement. It yields 7-azabicyclo[4.1.0]hepta-2,4-dienes (dihydrobenzazirines) and occurs with electron-accepting N-substituents [13]. An example is the conversion of 7 into 8 at -70°C in a proportion of 9 1. A trimethylene chain bridging the 2,7-positions favours the formation of dihydrobenzazirine (9), but a tetramethylene bridge that of azepine (10) ... 

Bridged saturated oxepin derivatives can be produced by oxyselenation of cyclo-octadienes and 5-hydroxycyclo-octenes, e.g. (136), via transannular attack of oxygen on a first-formed episelenium ion the product ratio is solvent-dependent. ... 

---