Lewis Acid-Catalyzed Divergent (4+3)/(4+2) Annulations of o-Quinone Methides with Bicyclo[1.1.0]butanes Lead to sp(3)-Rich Oxabicyclic Frameworks

路易斯酸催化的邻醌甲化物与双环[1.1.0]丁烷的发散型(4+3)/(4+2)环化反应生成富含sp(3)杂化的氧杂双环骨架

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Abstract

Benzannulation strategies that attach a planar arene ring to cyclic, saturated, three-dimensional bridged motifs are becoming valuable for drug discovery. Herein, a Lewis acid-catalyzed [4+3] annulation of in situ-generated o-QMs with bicyclo[1.1.0]butanes is developed. Reaction modulation further leveraged a telescoped [4+2] annulation of o-QMs with the in situ-formed cyclobutanes, leading to diversified sp(3)-rich oxabicyclic architectures. Overall, this study expands the scope for a new bioisosteric space for medicinal chemistry.

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