Unlocking Tertiary Halides from Primary Alkylamines through Deamination

Abstract Selective halogenation at sterically congested alkyl centers remains a long-standing challenge due to limited steric accessibility and the lack of general approaches. Deaminative strategies offer a powerful solution, leveraging the abundance of primary alkylamines in synthetic and bioactive molecules. In this context, O-diphenylphosphinylhydroxylamine enables transient amine-to-radical conversion, allowing efficient installation of Cl, Br, and I at otherwise inaccessible tertiary carbon centers. The method operates across highly hindered scaffolds—including bicyclo[1.1.1]pentane, cubane, and aza-bicyclo[2.1.1]hexane frameworks—demonstrating that native alkylamines can serve as programmable entry points for functionalizing saturated, sterically encumbered sites. This advance establishes deaminative logic as a versatile blueprint for accessing halogenated, saturated architectures beyond the reach of conventional approaches.