Synthetic studies on bafilomycin A1: stereoselective synthesis of the enantiopure C1–C11 fragment

The synthesis of the enantiopure C1–C11 fragment of bafilomycin A1 has been achieved with a 4% overall yield over 18 steps from (R)-(+)-citronellol. Key steps involve Sharpless asymmetric epoxidation, Miyashita reaction of a γ,δ-epoxymethacrylate with trimethylaluminum in the presence of water, bis-OTMS selective Swern oxidations, Corey–Fuchs alkyne formation, Negishiʹs carbometalation, and stereoselective formation of the C2–C3 trisubstituted bond of the conjugated diene by a Wittig-type olefination of the α,β-unsaturated C3–C11 aldehyde with the ylide derived from the readily available phosphonium salt [Cl−, Ph3P+CH(OMe)COOMe].