Fully reagent-controlled asymmetric synthesis of (-)-spongidepsin via the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)

The ZACA reaction has been shown to proceed satisfactorily with internally OH-substituted 1-alkenes, provided that the OH group is unprotected and non-allylic. This reaction was used for reagent-controlled asymmetric construction of 3. Allylic alcohol was converted to 2 in seven steps via iterative ZACA processes and simple chromatography. (-)-Spongidepsin (1) was synthesized by using 2 and 3 through application of the esterification-amidation-ring-closing metathesis protocol previously reported.