Photoinduced Copper‐Catalyzed Stereoselective C(sp ³ )‐H Amination Enabled by Preorganized Multiple Noncovalent Interactions

Chiral α ‐amino cyclic amines are essential bioactive molecular skeletons that play a crucial role in regulating the biological functions of diverse molecules. Despite their significance, the asymmetric C─H amination of saturated cyclic amines using readily available nitrogen sources has not been accomplished. In this work, a photoinduced copper‐catalyzed highly enantioselective α ‐C(sp 3 )‐H amination of cyclic amines with pharmaceutically valuable aromatic and α , β ‐unsaturated amides is developed. In addition to amides, diverse aromatic N ‐heterocycles, as well as the unstable and challenging imine, can also participate in the reaction, delivering various functionalized α ‐amino cyclic amines with high diastereoselectivity. Mechanistic study and DFT calculation indicate that the C─N bond is formed through the radical addition of α ‐amino radical to Cu(II)‐amide species followed by the inner‐sphere reductive elimination. The preassembly of ( R )‐BINOL with the BOPA‐copper(II) benzamide via hydrogen bonding and CH···π interactions can enhance the stereoselectivity through exclusive π···π stacking interaction in ( R )‐pathway. The unique reaction model featuring photoredox transition‐metal catalysis, radical cross‐coupling, and multiple noncovalent interactions is the key to success of this chemistry.