Nickel‐Catalyzed Hydroamination of Olefins Utilizing Isoxazole as an <scp> NH ₃ </scp> Surrogate for the Synthesis of Aliphatic Primary Amines

Comprehensive Summary Aliphatic primary amines widely occur in pharmaceuticals, natural products, and bioactive compounds and serve as indispensable building blocks in organic synthesis. Alkene hydroamination enables the straightforward synthesis of amines from inexpensive and readily available alkene feedstocks; however, the efficient and selective construction of aliphatic primary amines via this strategy remains a formidable challenge. Herein, we developed a nickel‐catalyzed umpolung hydroamination of olefins using 5‐methoxy‐3‐phenylisoxazole as a sustainable and recyclable NH 3 surrogate for the convenient synthesis of aliphatic primary amines. This earth‐abundant metal‐catalyzed protocol displays broad substrate scope and good functional group tolerance, accommodating aryl alkenes, cyclic alkenes, unactivated aliphatic alkenes and internal alkenes under mild reaction conditions. The enamine intermediates undergo mild hydrolysis to afford aliphatic primary amines, with the released phenylacetoacetate to be recyclable to regenerate the isoxazole reagent. Additionally, asymmetric catalytic hydroamination of alkenes has also been achieved to afford chiral amine derivatives with moderate to good enantioselectivities (up to 96% ee). Mechanistic studies support a NiH‐catalyzed umpolung three‐component hydroamination pathway.