Bridge Heteroarylation of Bicyclo[1.1.1]pentane Derivatives

Herein we report the decarboxylative Minisci heteroarylation of bicyclo[1.1.1]pentane (BCP) derivatives at the C2 (bridge) position. The developed process directly couples free BCP C2-carboxylic acids with non-prefunctionalised heteroarenes to provide rare examples of polysubstituted BCPs in synthetically useful yields. An extension of the methodology to the related 2-oxa-bicyclo[2.1.1]hexane motif was also achieved. Finally, the impact of the BCP core on the physicochemical properties of a representative example compared to its all-aromatic ortho- and meta-substituted analogues was evaluated.