Asymmetric Inverse-Electron-Demand Diels–Alder Reaction of 2-Pyrones with Acyclic Indolyl Alkenes for the Synthesis of Chiral <i>N</i> -Alkylindoles

For the first time, this study employed a series of acyclic indolyl alkenes as dienophiles and successfully developed their inverse-electron-demand Diels-Alder (IEDDA) reactions with 2-pyrones, thereby constructing chiral <i>N</i>-alkylindole compounds bearing four chiral carbon centers. With an easily accessible BOX ligand, we achieved Zn-catalyzed IEDDA reactions of <i>N</i>-vinyl indoles and <i>N</i>-alkenyl indoles with 2-pyrones. Alternatively, under copper catalysis, the IEDDA reactions of <i>N</i>-styryl indoles with 2-pyrones were also developed. All reactions exhibited excellent regioselectivity (only one isomer), diastereoselectivity (dr >95:5), and enantioselectivity (up to 99% ee).