Enantioselective construction of cis -hydroindole scaffolds via an asymmetric inverse-electron-demand Diels-Alder reaction: application to the formal total synthesis of (+)-minovincine.

cis -Hydroindole scaffolds widely exist in a large number of natural products, pharmaceuticals, and organocatalysts. Therefore, the development of efficient and enantioselective methods for the construction of cis -hydroindoles is of great interest and importance. Herein, a novel approach for the enantioselective synthesis of cis -hydroindole scaffolds has been realized through a chiral N , N '-dioxide/Mg(OTf) 2 complex catalyzed asymmetric inverse-electron-demand Diels-Alder (IEDDA) reaction of 2-pyrones and cyclic enamines. A series of substituted cis -hydroindole derivatives bearing multiple contiguous stereocenters and functional groups were obtained in good to excellent yields and enantioselectivities (up to 99% yield, and 95% ee) under mild reaction conditions. Moreover, the enantioselective formal total synthesis of (+)-minovincine was concisely furnished with high efficiency and stereoselectivity to demonstrate the synthetic potential of this method.