Analysis of the Structure as a Whole

The three variations of the retrosynthetic analysis of quadrone discussed in the preceding section were based upon one general concept the sequential bond-after-bond disconnection of the core of the target molecule into a set of smaller fragments. Logistically it is an absolutely reliable approach a consistent 

The tricyclic precursor 87b was easily obtained from 87a in two steps in an overall 90% yield. The condensation of 87b and 88b via a Friedel-Crafts reaction, followed by an intramolecular Michael addition and oxidation, led to a one-pot formation of the intermediate pentacyclic product 89 in ca. 30% yield. The conversion of 89 into 83 was accomplished by standard procedures of oxidation and demethylation. 

In accordance with this plan, the target tricyclic system 92 was assembled in three reactions a Diels-Alder cycloaddition of the 2,5-dimethylbenzoquinone 96 and cyclopentadiene 95 to give 94 (quantitative yield) an intramolecular [2 4- 2] cycloaddition leading to 93 (85% yield) and finally, a quantitative conversion of the latter intermediate into the desired tricyclic system 92 by a [2 4- 2] cycloreversion under thermolysis conditions.Thus the closure of the cyclobutane ring proceeds with the formation of two vertical bonds, and C -C, while its cleavage involves the breakage of its two horizontal bonds, C -C. The net outcome of these two reactions corresponds to the most unusual isomerization of 94 into 92. 

This retrosynthetic analysis corresponds to a somewhat bizarre disconnection of the target structure 92 into a pair of strange C5 (95a) and Cg (96a) synthons. 

Of course, such an effective windfall upon retrosynthetic analysis does not happen very often. Nevertheless, it is generally recommended that the retro-synthetic analysis of polycyclic structures should be directed first to the search of pathways that lead to one stroke framework assemblage. These possibilities can usually be accomplished with the help of cycloaddition reactions. In the course of the initial analysis, special emphasis should be given to identify structural features of the strategic core which might lead to the use of cycloaddition transforms. Let us examine a few more examples that illustrate the fruitfulness of such a retrosynthetic beginning. 

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