A NiH-catalyzed migratory hydroalkylation of alkenyl amines with predictable and switchable regioselectivity is reported. By utilizing a ligand-controlled, directing group-assisted strategy, various alkyl units are site-selectively installed at inert sp 3 CÀ H sites far away from the original C=C bonds. A range of structurally diverse α-and β-branched protected amines are conveniently synthesized via stabilization of 5-and 6-membered nickelacycles respectively. This method exhibits broad scope and high functional group tolerance, and can be applied to late-stage modification of medicinally relevant molecules.

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Transition-metal-catalyzed remote hydrofunctionalization of alkenes remains an efficient but challenging protocol in chemical synthesis. Herein, we reported a ligand-controlled, directinggroup-assisted strategy to promote NiH-catalyzed site-selective (α, β, or γ) hydroamination of unactivated alkenes with weakly coordinating amide groups. The key to success lies in the employment of proper yet commercially available bidentate nitrogen-containing ligands, which enables delivery of 1,1-, 1,2-, and 1,3-diamines with good-to-excellent regioselectivity starting from the same substrates. A broad range of Obenzoylhydroxylamine electrophiles with different functional groups can be installed via Ni migration or nonmigration. Moreover, these predicable and positionally selective protocols provide a method for the enantioselective synthesis of highly valued 1,2diamines (via remote aliphatic C−H amination) and 1,3-diamines.

Comprehensive Summary Directing group‐assisted, transition metal‐catalyzed three‐component difunctionalization of alkenes has emerged as a powerful tool to drive molecular complexity. However, this strategy generally works with the substrates bearing directing groups in close proximity to the alkene moieties, due to the preference for formation of kinetically stable five‐membered metallacycles. Herein, we have disclosed a complementary strategy to accomplish a nickel‐catalyzed remote arylalkylation of alkenyl amines with excellent regioselectivity and diastereofidelity, involving rare six‐ or seven‐membered metallacycles. This general protocol is compatible with a series of δ‐ and ε‐alkenyl amines, providing corresponding valuable δ,ε‐ and ε,ζ‐difunctionalized aliphatic amines that would be difficult to synthesize. The coordination of the bidentate picolinamide auxiliary and the facile oxidative addition of alkyl halides to Ni(I) species are the key to the success of the developed remote olefin dicarbofunctionalization.