Synthetic Approaches to Polar Antimalarial 1,2,4-Trioxanes from C5-Aldehyde and Ipsdienol

The 4-acetoxy-substituted tiglic aldehyde (C5-aldehyde) 1 is unreactive under singlet oxygen photooxygenation conditions. When converted into the corresponding ester-alcohol 3, the photooxygenation led to an allylic hydroperoxide 4 which was converted into a series of 1,2,4-trioxanes 5 by BF3-catalyzed peroxyacetalization. A similar approach to polar peroxides started from the terpene alcohol ipsdienol and offered a new route to mixed trioxane-endoperoxides 11.