Lewis Acid-Catalyzed Asymmetric [2σ + 2π] Cycloaddition Reactions of Bicyclo[1.1.0]butanes and Vinyl Azido/Diazo Compounds

The [2σ + 2π] cycloaddition reaction of bicyclo[1.1.0]butanes (BCBs) and alkenes is a powerful method to construct pharmaceutically valuable bicyclo[2.1.1]hexane (BCH) frameworks. Asymmetric strategies developed have enabled [2σ + 2π] cycloaddition reactions of electron-deficient alkenes. However, an effective approach for electron-rich alkenes remains to be realized. Here we report asymmetric [2σ + 2π] cycloaddition reactions of BCBs and electron-rich alkene moieties of vinyl azido and diazo compounds. The chiral Lewis acid-activated BCB ketone complexes are crucial for achieving the reactivity and enantioselectivity. This protocol allows for the synthesis of chiral BCHs featuring two to three quaternary carbon centers and α-chiral tertiary azido or diazo functionalities in up to 98% yield, >19:1 dr, and >99% ee. Broad substrate scope, gram-scale synthesis, and good functional group compatibility demonstrate the practicality for synthesizing complex bicyclic structures. Mechanistic studies reveal that the nucleophilic attack of electron-rich alkenes on the cyclobutyl cation intermediate is the rate-limiting step.