Remote Desaturation of Unprotected Amines and C─H Amination of Alkanes by Polarity‐Matched N‐Radical Cations

A CuCl‐catalyzed strategy enables practical, selective, and efficient δ desaturation of unprotected amines. These bifunctional molecules allow rapid conversion of simple amines to privileged heterocycles in medicine. The key radical relay mechanism is an interrupted Hofmann–Löffler–Freytag (HLF) reaction, which may now be carried out without protecting groups. Based on ‘radical polarity matching’ analysis, we show here that N‐radical cations are ideal intermediates for facilitating efficient and selective 1,5‐H‐atom transfer (HAT) of unprotected amines. Mechanistic probes illustrate the scope, rate, selectivity, and utility of these distal amino alkenes. Computational studies compare the importance of kinetic (radical polarity) over thermodynamic (bond strength) factors in predicting HAT reactivity. Extension to an intermolecular variant allows the direct, desaturative C─H amination of alkanes in a net triple C─H functionalization.