Oxepins cycloaddition with tetrazine

Interestingly, in the inverse-electron-demand Diels-Alder reactions of oxepin with various enophiles such as cyclopentadienones and tetrazines the oxepin form, rather than the benzene oxide, undergoes the cycloaddition.234 236 Usually, the central C-C double bond acts as dienophile. Oxepin reacts with 2,5-dimethyl-3,4-diphenylcyclopenta-2,4-dienone to give the cycloadduct 6 across the 4,5-C-C double bond of the heterocycle.234 The adduct resists thermal carbon monoxide elimination but undergoes cycloreversion to oxepin and the cyclopenta-dienone.234... 

An interesting and important reaction of oxepines is their participation as dienophiles in [2 -I- 4] cycloaddition with inverse electron demand. Using 1,2,4,5-tetrazines or 1,2,4-triazines bearing electron-withdrawing substituents as dienes, this reaction leads to dihydrooxepino[4,5-d]pyridazines (7) or dihydrooxepino[4,5-c]pyridines (8), each of which can be oxidized to corresponding oxepino[4,5-d]pyridazines (9) or oxepino[4,5-c]pyridines (10) the latter are converted by the treatment with an acid to cyclopenta[. 

The reaction of oxepin with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate affords a 2 1 mixture of products 9 a and 10, whose formation can be rationalized by a [4+2] and a [4 + 6] cycloaddition, followed by nitrogen extrusion.235 With 2,7-dimethyloxepin, only dimethyl 6,8-dime-thy 1-2.4a-dihydrooxepino[4,5-c/]pyridazine-l,4-dicarboxy late (9b) as product of the [4 + 2] cycloaddition can be isolated.235 236... 

The reaction of oxepin and 2,7-dimethyloxepin with dimethyl 3-cyano-l,2,4-triazine-5,6-dicarb-oxylate takes the same course as the cycloaddition to the tetrazine. Two different addition products 11a and 12 are obtained in the case of oxepin, whereas dimethyloxepin yields only the [4 + 2] adduct lib.235... 

Arene oxide-oxepin systems have also been reported to undergo [2 + 4] or [4 + 6] pericyclic cycloaddition reactions with heterocyclic dienes like the tetrazine 279 and the triazine 280. 65 Thus 86 96 reacts with 279 and 280 to yield the dihydrooxepino [4,5-d] pyridazine 281 and the oxepino [4,5-c] pyridine 282, respectively, via a [2 + 4] cycloaddition as well as the phthalazine 283 and isoquinoline 284, respectively, probably via a [6 + 4] cycloaddition reaction. However, 157 gives only 285 and 286 arising from a [2 + 4] cycloaddition reaction. 

---