Total Synthesis of Antimalarial Macrolide Strasseriolide A by Ni/Zr-Mediated Reductive Ketone Coupling

The total synthesis of the antimalarial macrolide strasseriolide A is described. We established two different synthetic approaches. The first approach involves intermolecular esterification and a challenging Ni/Zr/Cr-mediated reductive ketone coupling macrocyclization for the formation of the 18-membered ring. The second approach involves intermolecular Ni/Zr-mediated reductive ketone coupling and macrolactonization. Ni-catalyzed C(sp³)-C(sp²) cross-coupling of a vinyl halide with an alkyl halide was employed for fragment synthesis.