Diverse Synthesis of Arene‐Fused [n.1.1]‐Bridged Molecules via Catalytic Cycloaddition and Rearrangement Reactions

Although great advancement has been made in synthesis of 3D bridged bicyclic[n.1.1]‐bioisosteres, facile construction of 2D/3D merged molecules incorporating bridged rings, as novel chemical space in drug discovery, remains a significant challenge. Herein a collective, selective, and diversity‐oriented approach for up to 6 types of 2D/3D polycyclic scaffolds featuring bicyclo[n.1.1] substructure is reported. A boronyl radical‐catalyzed [2s+2p] cycloaddition between bicyclo[1.1.0]butanes and ortho‐quinone methides afforded spirocyclic compounds containing a bicyclo[2.1.1]hexane unit, which were used as intermediates for synthesis of three types of 2D/3D scaffolds via judiciously controlled Lewis acid‐catalyzed rearrangements. The reaction and rearrangement of para‐quinone methides worked analogously and provided another two polycyclic scaffolds.