Catalytic Formal 2π+2σ Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2‐Oxabicyclo2.1.1hexanes

摘要

Abstract Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF3‐catalyzed 2π+2σ cycloaddition of aldehydes with bicyclo1.1.0butanes (BCBs) to access polysubstituted 2‐oxabicyclo2.1.1hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp3‐rich bicyclic frameworks and the exploration of BCB‐based cycloaddition chemistry.