Write a retrosynthetic analysis of 3 -cyclobutyl-3-heptanol from starting materials containing four carbons or less. Strategy We apply the steps discussed for retrosynthetic analysis: Identify all possible strategic disconnections, then evaluate the relative merits of these disconnections. In this case, our evaluation has to take into account the restriction that starting materials contain four carbons or less. Solution
- Applying what we have learned so far, we can dissect the product retrosynthetically in three possible ways: $a, b$, and $c$.
- All of them break down the target into smaller fragments, but none of these schemes provides fragments of the stipulated size: four carbons or less. Thus, the resulting ketones contain seven or nine carbon atoms, respectively, requiring their independent synthesis from correspondingly smaller fragments.
- Because the ketone arising from pathway $b$ is too large to be put together directly from two four-carbon pieces, disconnections $a$ and $c$ appear best to pursue in our analysis. In both cases, we first need to take the retrosynthesis one step further, to the stage of the respective alcohols (which we know how to oxidize, Section 8-6). The alcohol structures can then be subjected to additional potential C-C disconnections (as indicated by the wavy lines):
In both cases, only one of those disconnections provides the required four- and three-carbon fragments.
- We have two perfectly reasonable solutions to our problem: one that introduces the cyclobutyl portion early and one that does so late. Is one preferable to the other? One may argue yes, namely, the second pathway. The strained ring is sensitive and subject to side reactions, so bringing it in late in the synthesis is advantageous.