Diverse Synthesis of Arene‐Fused [n.1.1]‐Bridged Molecules via Catalytic Cycloaddition and Rearrangement Reactions
Tao Yu, Xue Zhao, Zaicheng Nie, Lulu Qin, Zhengwei Ding, Liang Xu, Pengfei Li
Abstract
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.