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

Zhenhua Zhang,Giovanni Lonardi,Thomas Sephton,Yusuf C Guersoy,Chiara Stavagna,Giovanni Lenardon,Massimo Bietti,Daniele Leonori

Published 2025 in Nature

ABSTRACT

Amines are among the most common functional groups in biologically active molecules and pharmaceuticals1, 2–3, yet they are almost universally treated as synthetic end points4. 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(sp3)–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. A strategy is described making use of in situ activation of radical boron chemistry to convert amines to handles for cross-coupling, enabling a range of useful chemistries to make and modify drug-like molecules.

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