Total synthesis of zincophorin methyl ester. Stereocontrol of 1,2-induction using sterically hindered enoxysilanes

Abstract

Reported herein is the total synthesis of zincophorin methyl ester, a polyketide ionophore. Of particular interest is the use of sterically hindered nucleophiles to surmount the unfavorable stereochemical outcome, leading to acetate aldol adducts, in nucleophilic addition to the aldehyde derived from propionates. The approach is based on the addition of an enoxysilane (bearing a removable phenylselenide moiety) to generate selectively Felkin–Anh adducts in a BF3⋅OEt2-mediated Mukaiyama aldol reaction. Subsequent reduction of the selenide group led to the corresponding syn-aldol acetate motif, and this approach was applied to induce selectively the C12–C13 relationship of zincophorin.