Fluorination in superacids: a novel access to biologically active compounds

In HF-SbF₅, reaction of various alkaloids with NBS, NCS, H₂O₂ yields fluoroderivatives: anti-addition is observed at the C6C7 double bond with tabersonine, but a more complex reaction is operative with vindoline, leading to 7-substituted (Br, Cl, OH)-20-fluoro derivatives. A completely different reaction pathway is observed with bis indole alkaloids (vinblastine, anhydrovinblastine, vinorelbine) in HF-SbF₅. In the presence of NBS (or better of CCl₄ or CHCl₃), 20′,20′-difluoroderivatives are obtained. Vinflunine (20′,20′-difluoro-3′,4′-dihydrovinorelbine) has been selected for its promising antitumor activity.