Copper-Catalyzed Asymmetric Amino Lactonization of Alkenes: Direct Access to Enantioenriched 1,2-Alkylamino Alcohol Derivatives

High Resolution Image Download MS PowerPoint Slide We report an enantioselective copper-catalyzed amino oxygenation of alkenes, enabling direct access to chiral β-alkylamino lactones in up to 96% yield and 99% ee. In contrast to previous methods that introduced protected forms of amines, this method allows for the direct installation of electron-rich alkylamines through an umpolung process using O -acylhydroxylamines. Furthermore, a more atom-economic one-component protocol was developed by the use of alkenyl O -acylhydroxylamines. High efficacy and enantiocontrol of this reaction are achieved by identifying a readily accessible chiral copper-PyBox system and critical hydrogen-bonding interaction between the alkylamino radical and carboxylic acid. Featuring a broad substrate scope and good functional group tolerance, this method affords a rapid entry to a wide array of 1,2-alkylamino alcohol derivatives, such as β-alkylamino ethers and diversely functionalized β-alkylamino alcohols.