A Scalable Approach for the Synthesis of Epothilone Thiazole Fragment (C12–C21 unit) Via Wacker Oxidation

Abstract

A new scalable synthesis of the common thiazole fragment (C12–C21 unit) of epothilone family of molecules (epothilone A–D) has been developed via palladium-catalyzed Wacker oxidation as a key step using (S)-2,2,3,3,9,9,10,10-octamethyl-5-vinyl-4,8-dioxa-3,9-disilaundecane, which has been prepared from commercially available chiral synthon (R)-ethyl-4-cyano-3-hydroxybutanoate. Then further chemical modifications using Horner–Wadsworth–Emmons reaction and Wittig reaction result in the common thiazole fragment (C12–C21 unit) in good yields.