Catalytic Asymmetric Synthesis of 3,3′-Bisindoles Bearing Single Axial Chirality

Abstract

A catalytic asymmetric synthesis of 3,3'-bisindoles bearing single axial chirality has been established via chiral phosphoric acid (CPA)-catalyzed enantioselective addition reaction of 3,3'-bisindoles with ninhydrin-derived 3-indolylmethanols. The selection of ninhydrin-derived 3-indolylmethanols as suitable electrophiles is based on the consideration that the symmetric and bulky moiety of ninhydrin would increase the steric congestion around the axis to generate stable axial chirality and avoid the generation of central chirality. By this approach, a series of 3,3'-bisindoles bearing single axial chirality were synthesized via the dynamic kinetic resolution (DKR) process in generally acceptable yields and considerable enantioselectivities. In addition, an in-depth investigation on the property (stability and rotation barrier) of the synthesized axially chiral 3,3'-bisindoles was carried out, thus providing useful information on this class of axially chiral frameworks. This approach makes use of the strategy of dynamic kinetic resolution of 3,3'-bisindoles, therefore expanding the generality and applicability of this strategy for catalytic asymmetric synthesis of 3,3'-bisindoles bearing single axial chirality.