Regio- and Stereoselective Metal-Catalyzed Reactions and Their Application to a Total Synthesis of (−)-Dactylolide

Abstract Relying on the prowess of metal-catalyzed carbon–oxygen and carbon–carbon bond-forming reactions, a concise asymmetric total synthesis of (−)-dactylolide was achieved in a 13 step longest linear sequence. The formation of a 2,6-disubstituted tetrahydropyran core via sequential Alder-ene reaction and palladium-catalyzed π-allyl etherification, construction of Z -trisubstituted vinylboronate by Alder-ene reaction of a borylated alkyne and rhenium oxide-mediated unidirectional allylic transposition, are the salient features of this convergent synthesis. The macrocyclization by late stage ring-closing metathesis with concomitant installation of the trisubstituted double bond is another distinctive feature. Overall, this synthesis highlights a new strategy involving unparalleled bond disconnections compared with other reported approaches.