Phosphazene base-catalyzed hydroamination of aminoalkenes for the construction of isoindoline scaffolds: Application to the total synthesis of aristocularine

Abstract

A method for isoindoline synthesis via phosphazene base-catalyzed intramolecular hydroamination of aminoalkenes was developed. The reaction has a broad functional group tolerance, including for halide, cyano, and methoxy groups, and could also be used to synthesize tetrahydroisoquinoline, pyrrolidine, and piperidine. The method was used as a key step in the total synthesis of aristocularine in six steps in 35% overall yield. The strategy involved the construction of an isoindoline core through controlling the formation of the desired CN bond, with the relatively labile methoxymethyl group and arylbromide remaining intact.