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

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.