Diverse Synthesis of Arene-Fused [n.1.1]-Bridged Molecules via Catalytic Cycloaddition and Rearrangement Reactions
Tao Yu1,2, Xue Zhao3, Zaicheng Nie1
1Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, China.
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.
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