An efficient synthesis of bridged-bicyclic peroxides structurally related to antimalarial yingzhaosu A based on radical co-oxygenation of thiols and monoterpenes

Synthesis of β-sulfenyl endoperoxides 9 was achieved by a four component sequential free radical reaction based on the application of the thiol-olefin-co-oxygenation reaction to monoterpenes, followed by in situ treatment with triphenylphosphine. β-Sulfenyl endoperoxides 9 were oxidized with m-CPBA to β-sulfonyl endoperoxides 10. This process provides an efficient method for the preparation of peroxides containing the 2,3-dioxabicyclo[3.3.1]nonane system (2) characteristic of antimalarial agents of the yingzhaosu A (3) family. A simple NMR diagnostic tool for the identification of stereoisomers is described.