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 the spectrum of the aforementioned 3D polycyclic scaffolds.