Precise Distal B–H Bond Activation of <i>nido</i>-Carboranes by Copper Catalysis: Synthesis of Benzene Bioisosteres from Boron Clusters
Ningning Zhou, Hongyuan Ren, Xinrui Li, Jie Peng, Zhaofeng Sun, Hou‐Ji Cao, Deshuang Tu, Changsheng Lu, Hong Yan
Abstract
The exploration of innovative molecular scaffolds offers an exciting opportunity to venture into a previously unexplored chemical space. Boron clusters, such as carboranes, exhibit three-dimensional (3D) cage structures for exopolyhedral derivatization along multiple directions. This makes carboranes hold great potential as bioisosteric mimetics of benzene. However, the lack of efficient synthetic strategies for the regioselective functionalization of up to ten B–H sites has considerably hampered the broad application of carboranes as benzene bioisosteres. Herein, we report a novel reaction paradigm that involves copper-catalyzed precise carbene insertion into the nucleophilic remote B–H bond of nido -carboranes. The current protocol enables the synthesis of a series of multifunctionalized boron cluster derivatives for the construction of benzene bioisosteres. The reaction proceeds under mild conditions with rapid conversion and exhibits a broad substrate scope and excellent group tolerance. These features render the method highly adaptable for the development of boron-cluster-modified pharmaceuticals and trinity-type boron neutron capture therapy (BNCT) drug candidates. Additionally, high-performance carborane-based luminogens, which were facilely constructed by the developed reaction, exhibit multicolor emissions, high solid-state luminescence efficiency, and aggregation-induced circularly polarized luminescence (AI-CPL). This study not only demonstrates the potential of boron clusters as benzene mimetics but also opens new avenues for drug discovery and materials development.