Insights on Cubane Exploration: Synthesis, Functionalization and Viability

First synthesized by Phillip Eaton and Thomas Cole in 1964^[1], cubanes are unique scaffolds of theoretical and practical interest in the fields of material science and medicinal chemistry. In fact, during the last two decades, they have been widely incorporated into bioactive molecules and are often referred to as “ideal benzene bioisosteres”^[2,3]. From the ingenious and scalable synthesis envisioned by Chapman^[4], to novel methods on decarboxylative radical-radical cross-coupling, the present work aims to share experience and insights obtained throughout almost two years of preparing and functionalizing this core with the objective of incorporating it in the group’s drug discovery campaigns.