Total Synthesis of Bafilomycin A1

A convergent synthesis of bafilomycin A1 (see structure) is presented, and relies on the Zn(OTf)2-mediated diastereoselective addition of alkynes to aldehydes. The coupling of a complex enyne with a sensitive aldehyde in the key step, in combination with a novel strategy for a chemoselective trans-reduction of the enyne, establishes an alternative to standard palladium-catalyzed cross-coupling strategies for the formation of 1,3-dienes.