Asymmetric vicinal C(sp3)–H difunctionalization of saturated cyclic amines via synergistic photoredox, copper and chiral phosphoric acid catalysis

Abstract

Existing strategies are typically limited to modifying a C–H site (α or β-position) of saturated cyclic amines, but the asymmetric difunctionalization of vicinal C–H bonds remains a formidable challenge. To address this challenge, this work introduces a synergistic catalytic system that merges visible-light photocatalysis with asymmetric copper and chiral phosphoric acid catalysis. This system enables the enantioselective synthesis of ring-fused amine skeletons by activating vicinal C–H bonds in straightforward saturated cyclic amines. The reaction proceeds in good yields (up to 76%) and excellent enantioselectivity (up to 92% ee). This work describes detailed mechanistic studies that identify the specific dual chiral catalytic system that forms the basis for the enantioselectivity.