Studies towards the synthesis of epothilone A via organoboranes

Abstract

Studies towards the synthesis of epothilone A via organoboranes have been described. A modified procedure for the large-scale preparation of B-γ,γ-dimethylallyldiisopinocampheylborane from prenyl alcohol has been developed. This reagent, upon reaction with various aldehydes, provides the corresponding α,α-dimethylhomoallylic alcohols in high enantioselectivities. The application of this reagent for the synthesis of the C₁–C₆ subunit of epothilone has been demonstrated. Alternatively, inter- and intramolecular asymmetric reduction protocols have also been utilized for the synthesis of the C₁–C₆ subunit of epothilone A. The synthesis of the C₇–C₂₁ fragment of epothilone A involving asymmetric alkoxyallyl- and crotylboration using α-pinene-derived reagents has also been described.