Enantioselective (3 + 2) Cycloaddition of Oxazepines and Bicyclo[1.1.0]butanes Catalyzed by Chiral-at-Metal Rh(III) Complexes

Bicyclo[n.1.1] skeletons are valuable bioisosteres for aromatic rings in drug discovery, yet efficient and versatile asymmetric synthesis of chiral azabicyclo[2.1.1]hexanes (aza-BCHs) remains challenging. To address the unexploited cycloaddition strategy involving oxazepines and bicyclo[1.1.0]butanes (BCBs), we develop a chiral-at-metal Rh(III)-catalyzed enantioselective (3 + 2) cycloaddition. This protocol affords diverse chiral aza-BCH derivatives in 50–96% yields with up to 99% ee under mild conditions, providing facile access to such privileged three-dimensional skeletons. In addition, a scale-up experiment and the synthetic transformations of the cycloadducts further highlight the synthetic utility.