Palladium-Catalyzed C–C Arylation of Strained Azabicyclo[4.1.1]Octanols Enabled Multifunctionalized Azepine Synthesis

Azepine derivatives represent a privileged structural motif in numerous natural products and pharmaceuticals, exhibiting a diverse range of biological and medicinal properties. Herein, we report an efficient method for the synthesis of multifunctionalized azepines via strain-release-driven C-C cleavage of azabicyclo[4.1.1]octanols. The reaction proceeds through a palladium-mediated β-carbon elimination of the bridge bicyclic alcohols to generate an azepine-based alkyl palladium intermediate, which subsequently undergoes arylation with aryl bromides. The method features a broad substrate scope and functional group tolerance, accommodating complex aryl bromides derived from several bioactive compounds. Moreover, its synthetic utility is demonstrated by its application in the synthesis of structurally diverse cyclic compounds through further derivatizations.