A synthetic strategy to bridged 2,3,8-trioxabicyclo[3,3,1]nonane endoperoxides

As a part of our work in the development of novel antimalarials, we were interested in elaborating an appropriate synthetic strategy for the preparation of endoperoxide-containing bridged bicyclic scaffolds. Through a TMSOTf-promoted dehydrative cyclization strategy we synthesized 2,3,8-trioxabicyclo[3,3,1]nonane endoperoxides. Alkyl substituents at C4 of the bicyclic scaffold could be readily introduced through exposure to Grignard reagents.