Lewis acid catalysed rearrangements of unsaturated bicyclic [2.2.n] endoperoxides in the presence of vinyl silanes; access to novel Fenozan BO-7 analogues

Reactions of a series of unsaturated bicyclic [2.2.n] endoperoxides with allyltrimethylsilane in the presence TMSOTf or SnCl4 provides the cis-configured endoperoxides 9a–12. It is proposed that this novel reaction proceeds via attack of the allylsilane on the carbocation derived from heterolytic cleavage of the endoperoxide bridge. The reaction proceeds with a high degree of diastereoselectivity and we propose that the bulky –CH2SiMe3 substituent adopts an equatorial position in a product-like transition state. In contrast to Fenozan B0-7, these compounds displayed poor antimalarial activity versus chloroquine-resistant parasites in vitro.