Deaminative cross-coupling of amines by boryl radical β-scission.

Amines are among the most common functional groups in bioactive molecules and pharmaceuticals,1-3 yet they are almost universally treated as synthetic endpoints.4 Here we report a strategy that repositions native primary, secondary, and tertiary amines as handles for cross-coupling. The platform relies on in situ activation via borane coordination and exploits a copper catalytic redox system that generates amine-ligated boryl radicals, which undergo β-scission across the C(sp³)-N bond to release alkyl radicals. These intermediates engage in copper-catalyzed cross-couplings with a broad array of C-, N-, O-, and S-based nucleophiles. The method tolerates diverse amine classes, enables modular functionalization, and supports late-stage editing of complex drug scaffolds. In addition, amides can be incorporated into the manifold via reductive funneling. This work establishes a general approach to deaminative C-N bond functionalization and introduces a distinct approach for making and modifying druglike molecules.