Diversification of the Avarane Skeleton Toward Spiroetherone A

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 S N Ar 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.