Enantioselective cascade Michael addition/cyclization reactions of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized polycyclic spirooxindoles.

An unprecedented Zn(OTf)2-catalyzed asymmetric Michael addition/cyclization cascade of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles has been disclosed. This transformation provides an efficient access to various synthetically important polycyclic spirooxindoles in a highly stereoselective manner under mild conditions (72–99% yields, up to >95:5 d.r. and >99% ee). The reaction leads to the formation of three consecutive stereocenters, including 1,3-nonadjacent tetrasubstituted carbon stereocenters, in a single operation. A bifunctional activation model of the chiral Zn(OTf)2/bis(oxazoline) complex was proposed based on control experiments, wherein the ZnII moiety serves as a Lewis acid and the N atom of the free NH group acts as a Lewis base by a hydrogen-bonding interaction.