Allylic bromination of anhydrodihydroartemisinin and of its 10-trifluoromethyl analogue: a new access to 16-substituted artemisinin derivatives

The reactivity of the anhydrodihydroartemisinin 2 and of its 10-trifluoromethyl analogue 3 toward brominating reagents was explored with the aim of preparing the new corresponding C-16 allylic bromides 5 and 7. Both glycals 2 and 3 react with NBS to provide compounds 5 and 7, respectively. From the 10-CF3 anhydrodihydroartemisinin 3, the allylic bromination also occurred in high yield with Br2 in CCl4. Products 5 and 7 react with N-, O- and C-nucleophiles. From 5, products of SN and SN′ were obtained in low to moderate yield, while the CF3-substituted allylic bromide 7 only underwent nucleophilic substitution. New fluorinated 16-substituted artemisinin derivatives 14a–c could be obtained in high yield.