Cyclooctadiene-Derived Cage-Divergent Synthesis of Heteroadamantanes and Alternative Polycyclic Systems

We report a scalable, cage-divergent synthesis of oxygen- and nitrogen-doped adamantanes and related tricyclic morpholine mimetics from readily available cycloocta-1,5-diene. This approach enables multigram quantities of such products, which were previously hardly accessible or even unavailable, like promising tricyclic morpholine analog fixed in a boat conformation. Key cyclization steps were de novo optimized with accessible, greener, and safer rea-gents. The attempts for further functionalization underscored limitations, offering early insights into the potential utility of heteroadamantanes in medicinal chemistry and beyond.