Total Synthesis of Bafilomycin A 1

A convergent synthesis of bafilomycin A 1 , a potent inhibitor of V‐type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium‐catalyzed trans ‐reduction of the resulting propargylic enyne efficiently installs the required C10–C13 trans , trans ‐diene subunit, implementing an alternative strategy to traditional palladium‐catalyzed cross‐coupling strategies. A highly selective oxidation of a secondary hydroxyl group in a triol sets the stage for the completion of the synthesis.