Oxepine skeleton

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. 

A six-step synthesis of hexahydrofuro[3,2-3]oxepin-2(3/7)-one involves cyclization with the formation of an ethereal C-0 bond (Scheme 13). However, its specific peculiarities are that the product skeleton is built from tetrahydrofuran (THF) and furan, the key reactions being the oxidation of a furan ring with singlet oxygen, followed by an intramolecular Michael addition to 2(5/7)-furanone C=C bond <2003TL4467, 2004TL5207>. 

The maytolins are an interesting instance of new sesquiterpenes from the Celastraceae characterized by the presence of a tetrahydro-oxepine nucleus. It would seem that these new types of skeleton are only biosynthesized by species of the MORTONIA genus, which consists of just four species, endemic to Mexico and the southern Unites States. The chemical study of three of these four species led to the isolation and characterization of eight new sesquiterpenes [31-33](Figure3). 

Recently, Tu, Li, and coworkers [58] described the first domino [4-1-1]/ [3- -2- -l]/[5- -l] and double [4-1-3] cyclization reactions of o-phthalaldehyde 94 and 4-hydroxy-6-methyl-2H-pyran-2-one 95 with N-substituted enaminones 57 (Scheme 12.37). Using N-substituted 3-aminocyclohex-2-enones as enaminone led to pentacyclic pyrano[3, 2 2,3]indeno[2,l-c]pyridines 96 in 44-68% yield, whereas by employing N-substituted 4-aminofuran-2(5H)-ones the reaction occurred in another direction to form multifunctionalized pentacyclic pyrano[4,3- j]oxepines 97. This work provides an attractive strategy for the construction of structurally diverse pentacyclic oxa-azaspiro and oxa-azabridged skeletons. 

The cularines are a group of isoquinoline alkaloids with the general structure (1), which incorporates an oxepine system in its molecular skeleton. If the nitrogen is secondary the alkaloid can be called a norcularine. The occurrence of cularine alkaloids in nature seems to be associated mainly with the Fumariaceae family (Sham-ma 1972, Shamma and Moniot 1978). 

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