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

Abstract

Widely available cycloocta-1,5-diene (COD) serves as a highly versatile and convenient platform for cage-divergent synthesis of diverse three-dimensional frameworks. Here, we demonstrate streamlined, COD-based protocols delivering oxygen- and nitrogen-doped adamantane analogues and spherical morpholine mimetics in high yields (>70%) at multi-hundred-gram scale. These cost-efficient methods minimize steps and use inexpensive reagents, significantly improving scalability and operational simplicity. This approach unlocks further derivatization opportunities and exploration of chemical properties across a spectrum of the aforementioned 3D polycyclic scaffolds.