Ring synthesis Grob fragmentation

The total synthesis of the phenolic sesquiterpene (+)-parviflorine was accomplished by L.A. Maldonado and co-workers. The key step in the synthetic sequence was the reaction of an enamine with acrolein to form a bicyclic intermediate, which was subjected to a Grob fragmentation to afford the eight-membered ring of the natural product. The bicyclic ketone substrate was refluxed in benzene using a Dean-Stark trap and the resulting enamine was taken to the next step as crude material. 

In Grieco s synthesis of compactin, the required stereochemical information in the A ring was embedded in the oxabicyclic subunit of compound 225 [192]. Ring opening was induced by base promoted Grob fragmentation which generated formaldehyde and decalin 226, Eq. 138. 

Grob fragmentation reactions have proved useful in organic synthesis, as, for example, in the synthesis of compounds with larger rings (equation 10.11). ... 

In addition to their use as protecting groups, dioxolanes have been employed as intermediates. One example is a ring expansion of cyclopentanones via Grob fragmentation of the acetal (eq 14). A novel synthesis of glycerol from formaldehyde and ethylene glycol involves dioxolane intermediates. ... 

This reductive alkylation was used in a synthesis of 8, which contains the 10-membered ring system of germacrane sesquiterpenes. Thus the tetralonc 5 was converted by way of 6 into the tosylate 7. On treatment with LDA in THF at 24°, 7 underwent a Grob-type fragmentation to give 8. 

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