Photoinduced Copper-Catalyzed Stereoselective C(sp³)-H Amination Enabled by Preorganized Multiple Noncovalent...

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(sp³)-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.