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

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.