Unmasking Inherent Chirality Within the Cubane Skeleton

Cubane, a hexahedral hydrocarbon, can be converted into an asymmetric molecule with a minimum of three substituents. The resulting chiral cubane can be used as a pharmacophore or a chiral ligand. Starting from the cubane carboxamide, the 1,2,3-substituted compound was synthesized by sequential ortho-metalation. The 1,3,5-substituted compound was synthesized by combining site-selective halogenation and halogen-metal exchange and the resulting racemate was subjected to enantiomeric resolution by HPLC.