Formal [2σ +\n2σ]-Cycloaddition of Aziridines\nwith Bicyclo[1.1.0]butanes: Access to Enantiopure 2‑Azabicyclo[3.1.1]heptane\nDerivatives

Saturated nitrogen heterocycles are among the most significant\nstructural components in small-molecule pharmaceuticals. Herein, a\nprotocol for the construction of enantiopure 2-azabicyclo[3.1.1]­heptane\nderivatives by a stereospecific intermolecular formal cycloaddition\nof aziridines with bicyclo[1.1.0]­butanes is described. The reaction\nis run by using B­(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub> as a catalytic\nadditive to give access to a library of enantiopure 2-azabicyclo[3.1.1]­heptane\nderivatives (37 examples) under mild and operationally simple conditions.\nSuccessful scale-up reactions, mechanistic experiments, density functional\ntheory (DFT) calculations and synthetic applications are presented.