Three-Component Catalytic Amino Etherification of Alkenes: Enabled by Silyl Ether-Promoted C-O Coupling.

A three-component amino etherification of alkenes presents an ideal and direct strategy to access high-value 1,2-alkylamino ethers yet remains challenging. Herein, we disclosed a catalytic three-component amino etherification of alkenes that enables unprecedented incorporation of versatile aliphatic amines and structurally diverse alkyl or aryl ethers onto alkenes of various substitution patterns. The success of this method relies on a copper-catalyzed electrophilic amination of alkenes using O-benzoyl-hydroxylamines and the subsequent C-O bond formation using silyl ethers. Mechanistic studies further reveal the critical role of silyl ethers for an alkoxide transmetallation in the C-O coupling step, which guided us in further development of a more convenient protocol for amino oxygenation of alkenes directly using alcohols and phenols with an in situ silyl ether formation. This catalytic method has been successfully applied to the functionalization of a wide range of complex bioactive molecules such as terpenoids, amino acids, nucleobases, and various heterocycles, showing broad functional group compatibility and great potential for its application in synthetic and medicinal chemistry.

Duke Scholars

Author Qiu Wang Chemistry