Construction of Axially Chiral Indoles by Cycloaddition–Isomerization via Atroposelective Phosphoric Acid and Silver Sequential Catalysis

Axially
chiral indole-based frameworks occur in natural products,
bioactive molecules, and chiral ligands. Thus, the development of
catalytic asymmetric atroposelective approaches for de novo construction
of these frameworks is highly valuable. Here, the atroposelective
organo/metal combined dual catalysis strategy for de novo construction
of valuable axially chiral indole frameworks has been developed. This
protocol utilized a catalyst system of two chiral phosphoric acids
(1 mol %) in combination with AgNO3 (1 mol %) and was based
on the unreported intermolecular cycloaddition–isomerization
reaction of our recently introduced C-alkynyl N,O-acetals and 2-naphthylamines.
An important class of hitherto inaccessible axially chiral indoles
with a C–N axis were obtained in good yields and enantioselectivities.
The axially chiral indoles obtained also provided a platform for the
catalyst-controlled atroposelective synthesis of axially chiral indoles
bearing two C–N axes, which are difficult to access by the
existing methods. This work is also an example of 2-naphthylamines
used as 1,3-dinucleophiles and three-atom (CCN) synthons in cycloadditions.