Diastereodivergent Access to cis,cis- and cis,trans-Angular Triquinanes: Total Synthesis of (±)-Arnicenone

Angular triquinanes constitute an important class of polycyclic natural products characterized by compact, angularly fused ring systems and multiple contiguous stereocenters. Herein, we report a diastereodivergent strategy for stereocontrolled access to both cis,trans- and cis,cis-angular triquinanes from common allene precursors. The cis,trans-fused triquinanes were constructed through a Lewis acid-promoted intramolecular [3+2] Danheiser annulation, whereas the complementary cis,cis frameworks were accessed via photochemical [2+2] cycloaddition followed by oxidative ring expansion. Notably, substitution at the R1 position of the allene precursor reversed the diastereoselectivity of the [3+2] annulation, providing direct access to a cis,cis-angular triquinane. DFT calculations indicate that the initial spirocyclization governs both the reactivity and stereochemical outcome of the [3+2] pathway, with substrate-dependent steric interactions accounting for the observed diastereodivergence. The synthetic utility of this strategy was demonstrated through the total synthesis of (±)-arnicenone via the [2+2] cycloaddition/oxidative ring-expansion pathway, while an alternative synthesis from the cis,cis-[3+2] Danheiser annulation product further highlights the complementary nature of the two approaches. Together, these results establish a unified platform for stereodivergent access to angular triquinanes and their application to complex natural product synthesis.