Enantioselective Total Synthesis of Amphidinolide F

A common-intermediate approach is utilized in the total synthesis of amphidinolide F (see scheme, left) to access both the C1–C8 and the C18–C25 portions of the macrolide. A silver-catalyzed rearrangement/cyclization was employed to construct the two tetrahydrofuran rings. A Felkin-controlled, dienyl lithium addition to an α-chiral aldehyde incorporated both the C9–C11 diene and the alcohol at C8. An umpolung sulfone alkylation/oxidative desulfurization sequence is employed to couple the two moieties.