Trans Ring-fused endo system

In the trans ring-fused system, on the other hand, the very large reactivity difference suggests that the exo isomer 94 can react via a bisected conformation, but the endo isomer 93 may be forced into the less-favorable, close-to-perpendicular geometry. 

For the synthesis of the complex natural product, the terminus six-membered ketone 55 had to be transformed into an oxepane ring. For this necessary transformation, the authors were attracted by the single-carbon homologation of a pyr-anone (a sort of ring-expansion) because, in prindple, it could be used in an iterative sense at any stage of the 6-endo cydization in their poly-TH P-based synthetic approach for the synthesis of trans-fused 6,7,6 (THP-oxepane-THP) and 6,7,7 (THP-oxepane-oxepane) ring systems [28]. Treatment of ketone 55 with TMSCHN2... 

Stereochemistry for the cis-fused series in this system is readily specified by exo and endo. While there are two, relatively conformationally mobile rings present, this sytem is especially well behaved in terms of shift additivity. No significant quantity of data was found for trans-fused bicyclo[3.3.0]octanes. 

Both the cis- and trans-fused compounds represent valuable models for other, cyclohexane-based systems. Stereochemistry in the cis compounds is specified simply as exo and endo, while the orientations of groups in the trans series and those with a bridgehead double bond are specified based on their orientation as axial (A) or equatorial (E) substituents. Note that this system is distinct from that used with the trans-fused bicyclo[4.3.0]nonanes but it was felt that this inconsistency would be more than repaid here by the ease with which the spatial orientation of the groups could be visualized. Corresponding use of axial and equatorial for the [4.3.0]nonanes would have required new definitions of orientations of substituents on the five-membered ring. 

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