UCLA

Icosahedral carboranes, a class of boron-rich clusters, are kinetically stabilized by the multicenter-2-electron delocalized bonding mode. The resulting 3-dimensional σ-aromaticity of the carboranes are analogous to the two-dimensional aromaticity of benzene, yet sterically these clusters are more comparable to adamantane. The composition of carboranes which contains two carbon vertices and ten boron vertices contributes to the unique anisotropic σ-aromaticity. This anisotropic σ-aromaticity, combined with steric hindrance, make carboranes an interesting molecular scaffolding for medicinal chemistry research. In this thesis, starting from B(9) brominated o-and m-carboranes, a Pd-catalyzed cross-coupling strategy has been developed to incorporate a series of N-containing nucleophiles with diverse electronic properties. This advancement further enriches the library of carborane structures. By using a Pd-catalyzed cyanation of 9-bromo-m-carboranes established by our group, we have successfully introduced the carborane moiety into histone deacetylase inhibitor as a new three-dimensional capping group. Initial cell study has shown carbonyl inhibitors have similar or decreased toxicity compared to their adamantyl analog.