Photocatalytic Hydrogen Atom Transfer-Induced Arbuzov-Type α-C(sp3)-H Phosphonylation of Aliphatic Amines

Despite remarkable progress in photocatalytic hydrogen atom transfer (HAT)-induced C-(sp(3))-H functionalization, achieving C-(sp(3))-H to C-(sp(3))-P transformation by the HAT process remains highly challenging due to P-reagents' compatibility issues. alpha-Aminophosphonic acids have shown great potential in medicinal chemistry, yet their synthesis is hindered by limited substrate scopes, poor functional group tolerance, and reliance on prefunctionalized substrates, restricting their broad applications. Herein, we report photocatalytic HAT-induced alpha-C-(sp(3))-H phosphonylation of aliphatic amines, providing rapid access to structurally diverse alpha-aminophosphonates from abundant amines. Leveraging intramolecular HAT, radical polar crossover, and an Arbuzov-type phosphonylation cascade, the challenges associated with HAT-induced C-(sp(3))-H to C-(sp(3))-P transformation were overcome. This protocol features base-free, redox-neutral, and mild conditions and broad scopes, employing amines as limiting reagents, and allows for late-stage phosphonylation of complex drug molecules possessing amine moieties.