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Visible-Light-Induced Nitrogen-Atom Deletion of Unactivated Secondary Amines

Haojie Ji, Junying Zang, Panpan Ma, Hongjian Lu

2025Journal of the American Chemical Society7 citationsDOI

Abstract

Single-atom deletion has emerged as a powerful strategy for C–C bond formation, but existing methods are largely restricted to benzylic substrates, limiting their broader synthetic utility. Here, we report a visible-light-induced nitrogen-atom deletion of unactivated secondary amines. This transformation enables the efficient construction of general C(sp 3 )–C(sp 3 ) linkages directly from readily available C–N bonds, introducing atom deletion as a practical disconnection strategy in retrosynthetic design. The protocol applies to a wide range of N-heterocycles, converting them into the corresponding N-deleted carbocycles and heterocycles, and thereby streamlining access to pharmaceutically relevant yet previously inaccessible molecular scaffolds. Mechanistic studies reveal that visible light directly excites isodiazenes, redirecting their reactivity from N atom insertion toward N atom deletion. This discovery provides unprecedented control over isodiazene chemistry and unlocks opportunities for divergent skeletal editing. Overall, this work introduces a general platform for nonbenzylic C–C bond formation and a versatile approach to nitrogen-based skeletal editing, expanding the synthetic toolbox for organic synthesis, medicinal chemistry, and chemical biology.

Topics & Concepts

ChemistryRetrosynthetic analysisToolboxLimitingCombinatorial chemistryReactivity (psychology)Atom (system on chip)Chemical synthesisDrug discoveryDisconnectionStereochemistryComputational biologyAtom economyOrganic synthesisSketchNanotechnologyTransformation (genetics)CycloadditionRange (aeronautics)Radical Photochemical ReactionsPhotochromic and Fluorescence ChemistryClick Chemistry and Applications
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