Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone.

An efficient and highly enantioselective synthesis of tipranavir is realized based on an iridium-catalyzed asymmetric allylic substitution. High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% ), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic -butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% and >20:1 .