Deaminative cross-coupling of amines by boryl radical -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 -scission across the C(sp)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 CN bond functionalization and introduces a distinct approach for making and modifying druglike molecules."

A platform repositions native primary, secondary, and tertiary amines as handles for cross-coupling through in situ borane coordination. A copper catalytic redox system generates amine-ligated boryl radicals that undergo beta-scission across the C(sp)N bond to release alkyl radicals. The released alkyl radicals participate in copper-catalyzed cross-couplings with a broad range of C-, N-, O-, and S-based nucleophiles. The approach tolerates diverse amine classes, enables modular functionalization, supports late-stage editing of complex drug scaffolds, and allows incorporation of amides via reductive funneling to achieve deaminative C–N bond functionalization for druglike molecule modification.

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