Application of Tandem Ring-Closing Enyne Metathesis: Formal Total Synthesis of (−)-Cochleamycin A

Abstract

A tandem ring-closing metathesis of a silaketal-based dienyne substrate proceeded efficiently to provide a bicyclic siloxane, which upon removal of the silicon tether afforded an (E,Z)-1,3-dienediol. Further manipulation of this key functional motif rendered synthesis of the entire C1-C19 linear skeleton of (-)-cochleamycin A, a late-stage intermediate employed in the previous total synthesis of (+)-cochleamycin A by Roush and co-workers.