Salen-Ti-Catalyzed Formal [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Alkenes

Bicyclo[2.1.1]hexane (BCH) is a C(sp 3 )-rich bicyclic motif that has garnered significant interest as a bioisostere of ortho- and meta-substituted benzenes. However, the limited synthetic accessibility of BCH derivatives has hindered its broader application. We herein report a salen-Ti-catalyzed system for the efficient [2σ + 2π] cycloaddition of bicyclo[1.1.0]butane ketones with alkenes. This method is characterized by low catalyst loading, mild conditions, operational simplicity, and excellent functional group tolerance. These advantages make it a highly attractive strategy for pharmaceutical design and synthetic chemistry.