Disconnection of bridged rings

The individual bonds of a bridged ring system which are eligible for inclusion in the set of strategic bond disconnections are those which meet the following criteria. 

Two possible intramolecular disconnections are available for the [2.2.2] bicyclo-octane ring system (path A and path B, Scheme 1.4). The choice between the initial [4+2] disconnections A and B at first appears inconsequential leading to idealized intermediates of comparable complexity (54 and 57). However, when the [4+2] and [3+2] disconnections are considered in sequence, the difference becomes clear. For path A, retrosynthetic [3+2] disconnection of intermediate 54 leads to the conceptual precursor 56, which embodies a considerable simplification. In contrast, path B reveals a retrosynthetic [3+2] disconnection of intermediate 57 to provide the precursor 59, a considerably less simplified medium-ring bridged macrocycle. Thus, unification of the [3+2]/[4+2] dual cycloaddition strategy, using the staging... 

As in the case of acyclic compounds, the level of difficulty of the synthesis of a cyclic compound depends upon whether the molecule is a consonant or a dissonant system. However, some additional difficulties may be encountered in molecules with medium-sized rings as well as in polycyclic bridged compounds, which are treated in the next Chapter. On the other hand, as we have seen in Heading 4.3, even simple monofunctionalised cyclic molecules may require a FGA operation before bond disconnection of the cyclic network at the ipso-, a- or 13-positions can be effected. 

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