Cycloaddition of bicyclo[1.1.0]butanes with enamides for the efficient synthesis of 2-amino-bicyclo[2.1.1]hexanes

Here, we develop a mild and scalable approach for the synthesis of 2-amino-bicyclo[2.1.1]hexanes via Lewis acid-catalyzed (3+2) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with enamides. The practicality of this methodology has been demonstrated by scale-up reactions and product modifications, providing highly valuable aniline bioisosteres and structurally complex three-dimensional cyclic amines.