N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides

Abstract

Both the pyrroloindoline core and N –CF 3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N –CF 3 -containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N –CF 3 moiety with commercially available reagents N -halosuccinimide and Et 3 N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N –CF 3 -pyrroloindolines.