Asymmetric Inverse-Electron-Demand Diels-Alder Reaction of 2-Pyrones with Acyclic Indolyl Alkenes for the Synthesis of Chiral N-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 N-alkylindole compounds bearing four chiral carbon centers. With an easily accessible BOX ligand, we achieved Zn-catalyzed IEDDA reactions of N-vinyl indoles and N-alkenyl indoles with 2-pyrones. Alternatively, under copper catalysis, the IEDDA reactions of N-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).