Enantioselective synthesis of tryptanthrin derivatives enabled by an asymmetric aza-Friedel–Crafts reaction

Abstract

A highly enantioselective aza-Friedel–Crafts reaction of tryptanthrin-derived ketimines with indoles/pyrrole using chiral phosphoric acid as a catalyst has been established. This protocol allows the formation of a series of chiral tryptanthrin derivatives simultaneously bearing the privileged tryptanthrin and indole/pyrrole skeletons with excellent yields and good to excellent enantioselectivities (up to 99% yield, 99% ee). In particular, a preliminary biological evaluation showed the potential of the products for medicinal applications, with moderate to good cytotoxicity in vitro against leukemia cells.