Nickel-catalyzed C(sp2)–H bond aminoalkylation of alkenes and arenes for the synthesis of δ-amino acid derivatives

Abstract

We report a highly efficient Ni-catalyzed C(sp²)–H bond aminoalkylation strategy for the synthesis of optically pure amine-containing molecules. This protocol features straightforward operation, readily accessible chiral building blocks derived from natural α-amino acids, and compatibility with late-stage functionalization of drug molecules. Mechanistic investigations reveal a Ni(II)/Mn cooperative catalytic cycle, enabling cross-coupling with β-iodoalkylamines while effectively suppressing β-elimination side reactions. The method exhibits broad substrate scope for both aromatic amides and acrylamides, affording diverse δ-amino acid derivatives in moderate to excellent yields (42–99% yield, up to 99% ee). Notably, gram-scale synthesis and late-stage diversification of bioactive molecules (e.g., estrone, shikimic acid) underscore its synthetic utility.