Copper-Catalyzed Ring-Opening 1,3-Difunctionalization of N -Chloro- N -Cyclopropyl Amides

The selective functionalization of cyclopropylamines has long remained challenging due to their limited electronic bias and the difficulty of achieving efficient bond polarization. Here, we report a copper-catalyzed chloroamide-directed strategy that enables 1,3-difunctionalization of cyclopropylamides in a single step. This method leverages strain-driven single-electron reduction to generate nitrogen-centered radicals, which undergo rapid β-scission to produce versatile radical intermediates that can be efficiently intercepted by a broad range of nucleophiles. The approach provides modular access to α, γ-difunctionalized amines from simple precursors, features broad substrate scope including late-stage diversification of drug derivatives, and proceeds without the need for strong oxidants. By combining radical reactivity with a directing-group strategy, this atom-economical protocol establishes a general platform for constructing pharmaceutically relevant amine architectures and expands the synthetic utility of cyclopropylamines in synthetic and medicinal chemistry.