Direct Deaminative Halogenation at Hindered Tertiary Centers

General strategies for direct deaminative halogenation of α-tertiary amines─including those relevant to three-dimensional scaffolds─have remained an unsolved challenge in synthetic chemistry, primarily due to the difficulty of direct cleavage of C–N bonds at congested tertiary carbon centers. We report a radical-mediated deaminative halogenation platform that overcomes these limitations using commercially available O-diphenylphosphinyl hydroxylamine. By modulating reaction conditions, we redirect the inherent hydrogenation pathway toward halogen-atom transfer, enabling the efficient halogenation of sterically hindered substrates. This practical, one-pot transformation enables efficient chlorination, bromination, and iodination of structurally diverse amines while maintaining excellent functional group compatibility. The power of this methodology is also showcased by the straightforward preparation of valuable aryl-halide isosteres, including halogenated derivatives of bicyclo1.1.1pentane, bicyclo2.2.1heptane, bicyclo2.2.2octane, 2-azabicyclo2.1.1hexane, and cubane. Combining a broad substrate scope with operational simplicity and scalability, this advance provides a robust platform for late-stage molecular diversification and opens new avenues for the development of next-generation chlorine-containing drug candidates.