Rearrangements and Cyclizations of Natural Products

As early as 1893, it was discovered795 that camphor 185 rearranges to 3,4-dimethylacetophenone 186 in concentrated H2SO4 and the mechanism of the reaction 

However, Jacquesy and co-workers784,798 have shown that in superacidic HF SbF5 medium, the reaction takes a different course. Camphor gives a mixture of three ketones [Eq. (5.292)]. 

In a subsequent study, however, Whittaker and co-workers803 showed that the product formed from geraniol, in fact, is the isomeric bicychc ether 198. It was also shown that cyclization of citronellal in HSO3F— SO2 at 78°C affords pulegol and neoisopulegol that is, the transformation parallels closely the reaction in normal acids.804 

Whittaker and co-workers805,806 have also prepared a number of terpenoid bicyclic ethers, such as isomeric 1,6-dihydrocarveols 199 (HSO3F—S02,78°C) from unsaturated alcohols or diols.805 806pura-Menth-l-en-9-ol and a related diol afforded the seven-membered ring systems 200. The oxolane moiety in compound 201 was generated from the corresponding unsaturated alcohol precursor in 2 equivalents of triflic acid.807 

Fluorosulfuric acid is a widely used, highly effective reagent808 in electrophilic polyene cyclizations to synthesize fully cyclized compounds in a selective and stereospecific way. Furthermore, an internal nucleophile, most often oxygen, allows the construction of polycyclic skeletons with a heteroatom (vide supra). Snowden and co-workers809 transformed trienone 202 (a mixture of 4 diastereomers) into three isomeric irone derivatives [Eq. (5.293)]. Other acids gave inferior results. 

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