Deaminative cross-coupling of amines by boryl radical β-scission
Zhenhua Zhang, Giovanni Lonardi, Thomas Sephton, Yusuf C. Guersoy, Chiara Stavagna, Giovanni V. A. Lenardon, Massimo Bietti, Daniele Leonori
Abstract
Abstract Amines are among the most common functional groups in biologically active molecules and pharmaceuticals 1–3 , yet they are almost universally treated as synthetic end points 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 through borane coordination and exploits a copper catalytic redox system that generates amine-ligated boryl radicals, which undergo β-scission across the C( sp 3 )–N bond to release alkyl radicals. These intermediates engage in copper-catalysed cross-couplings with a broad range of C-based, N-based, O-based and S-based nucleophiles. The method tolerates diverse amine classes, enables modular functionalization and supports late-stage diversification of complex drug scaffolds. Also, amides can be incorporated into the manifold through reductive funnelling. This work establishes a general approach to deaminative C–N bond functionalization and introduces a distinct approach for making and modifying drug-like molecules.