Stereodivergent\nSynthesis of 6,12-Guaianolide C1 Epimers\nvia a Rationally Designed Oxy-Cope/Ene Reaction Cascade

Nature synthesizes epimeric C1 guaianolide congeners,\nkey components\nof major natural product classes, through a single structurally flexible\nmacrocyclic germacranolide core. Our rationally designed elemanolide-type\nscaffold (<b>5</b>) now mimics this natural process, enabling\nthe stereodivergent synthesis of both C1 epimers of 6,12-guaianolide\nlactone motifs. An oxy-Cope/ene cascade acts as the key step of this\nprocess, generating two distinct conformers of an intermediate germacranolide,\neach leading to a specific C1 epimer. Highly stereoselective redox\nmanipulations follow, culminating in the efficient syntheses of diverse\nosmitopsin-type guaianolides.