Diversification of the Avarane Skeleton Toward Spiroetherone A

Abstract

Studies toward spiroetherone A uncovered an unexpectedly rich reactivity landscape within the avarane skeleton. An intramolecular Michael addition onto a quinone enabled access to the characteristic spiroenedione core of the natural product. Alongside this transformation, diverse and unanticipated reaction pathways emerged, generating structurally complex molecular architectures. These included an unusual SNAr on an electron‐rich arene, a McMurry‐type ketone–ester coupling with concomitant reductive deoxygenation, or Wagner–Meerwein rearrangements furnishing oxaspiro[4.5]dienone and dihydrochromane scaffolds. As other divergent transformations developed, a (3 + 2) quinone monoacetal dimerization produced a dibenzofuran motif close to popolohuanone E, whereas a PIDA‐mediated alkene–phenol nitrile cyclization/Ritter reaction sequence delivered an unprecedented pentacyclic bridged imidate. This work demonstrates how synthetic exploration toward complex natural products can reveal unforeseen modes of reactivity and skeletal diversification.