Catalytic Atroposelective Synthesis of N–N Axially Chiral Indolylamides

The catalytic atroposelective synthesis of N–N axially chiral indolylamides was established via dynamic kinetic resolution, which makes use of chiral Lewis base-catalyzed asymmetric acylation of N-acylaminoindoles as a new type of platform molecule with anhydrides. By this strategy, a series of N–N axially chiral indolylamides were synthesized in overall good yields (up to 98%) with excellent enantioselectivities (up to 99% ee). Moreover, some of these N–N axially chiral indolylamides display some extent of anticancer activity, which demonstrates their potential application in medicinal chemistry. Therefore, this work has not only provided a new strategy for the synthesis of N–N axially chiral monoaryl indoles but also offered a new member of N–N axially chiral monoaryl indoles with configurational stability and promising application, thereby solving the challenges in atroposelective synthesis and application of N–N axially chiral monoaryl indoles.