Asymmetric synthesis of polycyclic spiroindolines via the Dy-catalyzed cascade reaction of 3-(2-isocyanoethyl)indoles with aziridines

Abstract

The chiral polycyclic spiroindoline motif is a frequently occurring structural unit in various biologically active natural products and pharmaceutical agents. The development of facile and efficient methods for assembling such architecture from readily available starting materials is highly desirable. Herein, we report a tailored strategy to access such compounds through an asymmetric ring-opening/Friedel–Crafts/Mannich/desulfonylation cascade reaction. In the presence of the N,N′-dioxide–Dy(III) complex, various 2,2′-diester aziridines and 3-(2-isocyanoethyl)indoles were converted into tetracyclic spiroindolines in a highly diastereo- and enantioselective manner (41 examples, up to 88% yield, 97% ee). On the basis of the absolute configuration of the product and previous works, a possible catalytic cycle was proposed to understand the origin of stereocontrol.