Copper‐Catalyzed Three‐Component Selective 1,4‐Amino Oxygenation of 1,3‐Dienes

Abstract

Abstract Multicomponent difunctionalization of 1,3‐dienes has emerged as a promising strategy for rapid synthesis of valuable allylic compounds. Here, we report an unprecedented three‐component 1,4‐amino oxygenation of 1,3‐dienes, enabled by copper catalysis and strong Brønsted acid. The reaction engages a novel mechanism that merges umpolung electrophilic amination via copper(I)‐catalyzed formation of aminium radical cations and copper (II)‐mediated carbon‐oxygen bond formation with alcohols. The observed 1,4‐selectivity is modulated by noncovalent interactions of aminated allylic intermediates. This method presents broad synthetic utility and offers a rapid entry to ( E )‐1,4‐allylic amino ethers, which can be derivatized into various polyfunctional molecules with high stereocontrol.