{Reference Type}: Journal Article
{Title}: Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen-Substituted Bicyclo[1.1.1]pentanes.
{Author}: Livesley S;Sterling AJ;Robertson CM;Goundry WRF;Morris JA;Duarte F;Aïssa C;
{Journal}: Angew Chem Int Ed Engl
{Volume}: 0
{Issue}: 0
{Year}: Oct 2021 27
{Factor}: 16.823
{DOI}: 10.1002/anie.202111291
{Abstract}: Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane 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 [1.1.1]propellane 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 [1.1.1]propellane as a valuable strategy for accessing functionalised BCPs.