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 [2σ+2π] cycloaddition between bicyclo[1.1.0]butanes and ortho-quinone methides afforded spirocyclic compounds containing a bicyclo[2.1.1]hexanes 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.