Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone
Wenhao Gan1, Minghui He1, Yeting Huang1
1School of Biological and Chemical Engineering, Zhejiang University of Science & Technology, 318 Liuhe Road, Hangzhou 310023, P. R. China.
Abstract:
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% ee), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic tert-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% ee and >20:1 dr.
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