Divergent polarity synthesis of glycosyl bicyclo[1.1.1]pentanes enabled by unified electrochemical difunctionalization of [1.1.1]propellane

Over the last decade, bicyclo[1.1.1]pentanes (BCPs) have emerged as valuable bioisosteres of aromatic rings, offering unique three-dimensional architectures for medicinal chemistry. Meanwhile, glycosyl derivatives play a pivotal role in chemical biology and drug discovery due to their widespread presence in biologically active molecules, however, the potential of bicyclo[1.1.1]pentanes (BCPs) as versatile scaffolds in glycoscience remains largely unexplored. Herein, we report a unified electrochemical strategy for the divergent polarity synthesis of BCP–glycosides via the difunctionalization of [1.1.1]propellane. By leveraging an electrochemical halogen-atom transfer (e-XAT) process, we achieve a one-step, three-component reaction of glycosyl bromides, [1.1.1]propellane, and radical acceptors under mild conditions, enabling the direct and polarity-divergent construction of glycosyl BCP–iodides, –hydrides, and –pinacolboronates (Bpins) with exceptional functional group tolerance and scalability. Mechanistic studies suggest that the electrochemical process facilitates the generation of key radical intermediates, which undergo selective addition to [1.1.1]propellane, followed by trapping with radical acceptors. This study discloses a unified electrochemical strategy for the polarity-divergent synthesis of BCP–glycosides, establishing a versatile platform for late-stage functionalization and streamlined access to privileged scaffolds in drug discovery and chemical biology.