%0 Journal Article
%T Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen-Substituted Bicyclo[1.1.1]pentanes.
%A Livesley S
%A Sterling AJ
%A Robertson CM
%A Goundry WRF
%A Morris JA
%A Duarte F
%A Aïssa C
%J Angew Chem Int Ed Engl
%V 0
%N 0
%D Oct 2021 27
%M 34705316
%F 16.823
%R 10.1002/anie.202111291
%X 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.