γ-Selective C(sp3)–H amination via controlled migratory hydroamination

Abstract Remote functionalization of alkenes via chain walking has generally been limited to C(sp 3 )–H bonds α and β to polar-functional units, while γ -C(sp 3 )–H functionalization through controlled alkene transposition is a longstanding challenge. Herein, we describe NiH-catalyzed migratory formal hydroamination of alkenyl amides achieved via chelation-assisted control, whereby various amino groups are installed at the γ -position of aliphatic chains. By tuning olefin isomerization and migratory hydroamination through ligand and directing group optimization, γ -selective amination can be achieved via stabilization of a 6-membered nickellacycle by an 8-aminoquinoline directing group and subsequent interception by an aminating reagent. A range of amines can be installed at the γ -C(sp 3 )–H bond of unactivated alkenes with varying alkyl chain lengths, enabling late-stage access to value-added γ -aminated products. Moreover, by employing picolinamide-coupled alkene substrates, this approach is further extended to δ -selective amination. The chain-walking mechanism and pathway selectivity are investigated by experimental and computational methods.