Chao Dong, Yihan Zhang, Chunyang Zhao, Jin He, Yingjie Liu, Ting Wang, Junkai Fu
ABSTRACT Regiocontrol represents a central challenge in the difunctionalization of unsaturated hydrocarbons. Achieving regioselectivity reversal can unlock structurally diverse molecules from common precursors, yet it is often disfavored by inherent kinetic and thermodynamic preferences. Herein, we report a three‐component aminative difunctionalization of 1,3‐dienes enabled by a newly developed Cu/La cocatalytic system that redirects the prevailing 1,2‐addition manifold to a regiospecific 1,4‐addition pathway. Both terminal and internal dienes, as well as 1,3‐butadiene derivatives, are compatible, with excellent functional group tolerance even toward NH and free hydroxyl groups. A broad range of oxygen‐based nucleophiles, including H 2 O, alcohols, and carboxylic acids, along with a biologically relevant fluorine atom, are all efficiently incorporated, yielding 1,4‐allylic amino alcohols, ethers, esters, and fluorides. Mechanistic experiments support a radical‐polar crossover pathway initiated by copper‐mediated generation of an aminyl radical cation (ARC) and indicate that steric modulation by the lanthanide salt is decisive in enforcing 1,4‐regioselectivity.