Enantioselective Dearomatizing Formal (3+3) Cycloadditions of Bicyclobutanes with Aromatic Azomethine Imines: Access to Fused 2,3-Diazabicyclo[3.1.1]heptanes

Although cycloadditions of bicyclobutanes (BCBs) have emerged as a reliable approach for producing bicyclo[n.1.1]alkanes such as azabicyclo[3.1.1]heptanes (aza-BCHeps), serving as saturated bioisosteres of arenes, the catalytic asymmetric variant remains underdeveloped and presents challenges. Herein, we developed several Lewis acid-catalyzed systems for the challenging dearomatizing (3+3) cycloaddition of BCBs and aromatic azomethine imines. This resulted in fused 2,3-diazabicyclo[3.1.1]heptanes, introducing a novel chemical space for the caged hydrocarbons. Moreover, an asymmetric Lewis acid catalysis strategy was devised for the (3+3) cycloadditions of BCBs and N-iminoisoquinolinium ylides, forming chiral diaza-BCHeps with up to 99% yield and 97% ee. This work represents the first successful demonstration of asymmetric (3+3) cycloaddition by introducing a chiral environment through the activation of BCBs.