Substituted oxepines

A variety of substituted oxepins and 1-benzoxepins can be converted to 2-oxabicyclo[3.2.0]hep-tadiene structures 2208 and 388-174.i82,i92.208-2ii irracjiation. 

Since both oxepin and its valence isomer benzene oxide contain a x-tb-diene structure they are prone to Diels-Alder addition reactions. The dienophiles 4-phenyl- and 4-methyl-4//-l,2,4-triazole-3,5-dione react with substituted oxepins at room temperature to give the 1 1 adducts 7 formed by addition to the diene structure of the respective benzene oxide.149 190,222... 

Summary of synthetic routes to benzo-, mono- and di-substituted Oxepins 583... 

The nature and position of substitution has a profound influence upon the oxepin-arene oxide equilibrium position. The effect of substituents on the relative energies of each valence tautomer has been calculated (80JA1255) and these theoretical results are in accord with the limited experimental data which are available. In general terms, oxepins substituted at the 3-position are less favored than the corresponding arene oxides, while the reverse obtained for 2- and 4-substituted oxepins. This substituent effect has been rationalized in terms of a preference for the maximum number of alternative resonance contributors. The influence of both 7r donating and v withdrawing substituents oh the oxepin contribution is summarized in Scheme 2. This latter effect may be considered as an electronic substituent effect. 

With minor variations on the haloepoxide route a remarkable number of mono- and di-substituted oxepins have been prepared and are included in Table 8. The electron donating or withdrawing capacity of substituent X present in the diene precursor will determine which bond will be more readily epoxidized or brominated (Scheme 33). 

Oxepanes, Oxepins, Thiepanes and Thiepins Table 8 Synthetic Routes to Benzo-, Mono- and Di-substituted Oxepins... 

Using both semi-empirical and ab initio calculations the study of oxepin (6), benzene oxide (7), and their equilibrium (Scheme 2) has been conducted. The fully optimized geometry (90MI902-01) agrees with that experimentally found for several substituted oxepines. The carbon skeleton of benzene oxide is practically planar while the angle between the epoxide ring and the adjacent plane is ca. 106°. The oxepin molecule is boat-shaped with a fold angles between C2—C7 and C3—C6 of ca. 137 and 159°, respectively. 

Aminomethyl)biphenyl-2-carboxylic acid (70) and -acetic acid (69) have been prepared from dibenzo-substituted oxepin-2-one 66 by potassium phthalimide ring opening. Further Arndt-Eistert homologation of 67 provided 68.[104]... 

Thermolysis of another cyclobutafuran derivative (Equation 40) leads to a substituted oxepine <2002JA7395>. 

An interesting approach to the substituted oxepine 102 has been described involving thermolysis of the bicyclic system 101, obtained from the rhenium complex 100 (Melm = N-methylimidazole Tp = hydridotris(pyrazolyl)borate) [02JA7395],... 

A substituted oxepin 328 can be prepared by the thermolysis of a cyclobuta[7]furan derivative 327 (Scheme 166) . 

Ring-closing olefin metathesis has been extended to vinyl chloride precursors, resulting, for example, in the preparation of the chloro-substituted oxepine derivative 43 from 42 in high yield (88%) <030L2505>. 

While the ferf-butyl substituted oxepins 96-98 result from the acid-catalyzed dehydration of a series of 1,4-disubstituted 2,6-diferf-butyl-2,5-cyclohexadiene-l,4-diols, this route is of limited synthetic value for arene oxide-oxepins. Ring expansion of a pyrylium salt using ethyl lithio diazoacetate and a Pd complex proceeds via a carbene intermediate to yield arene oxide-oxepin 99. Due to severe nonbonding interactions between the Bu groups, the oxepin valence tautomer only was observed. ... 

A thermal rearrangement of 7-oxabenzonorbornadienes mounted on a [3]polynorbornane bis-imide molecular rack has been shown to yield an oxepine using flash vacuum pyrolysis (13TL5335). Substituted oxepin-3(2Ji)-ones 67 have been shown to result from a tandem conjugate addition-alkylation-isomerization process between 1,2-allenic ketones 65 and ethyl 4-chloroacetoacetate 66 (13RA4156). 

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