Electrophilic Activation of 1.1.1Propellane for the Synthesis of Nitrogen‐Substituted Bicyclo1.1.1pentanes

Strategies commonly used for the synthesis of functionalised bicyclo1.1.1pentanes (BCP) rely on the reaction of 1.1.1propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to the facile decomposition of BCP cations, which has severely limited the applications of this strategy. Herein, we report the electrophilic activation of 1.1.1propellane in a halogen bond complex, which enables its reaction with electron-neutral nucleophiles such as anilines and azoles to give nitrogen-substituted BCPs that are prominent motifs in drug discovery. A detailed computational analysis indicates that the key halogen bonding interaction promotes nucleophilic attack without sacrificing cage stabilisation. Overall, our work rehabilitates electrophilic activation of 1.1.1propellane as a valuable strategy for accessing functionalised BCPs.