Accessing indole–isoindole derivatives via palladium-catalyzed [3+2] cyclization of isocyanides with alkynyl imines

Abstract

A facile protocol for the preparation of indole–isoindole derivatives was developed and proceeds via a palladium-catalyzed [3+2] cyclization of isocyanides with alkynyl imines. In this transformation, the palladium catalyst has a triple role, serving simultaneously as a π acid, a transition-metal catalyst and a hydride ion donor, thus enabling the dual function of isocyanide both as a C1 synthon for cyanation and a C1N1 synthon for imidoylation. Significantly, the reaction is the sole successful example for accessing indole–isoindole derivatives, and will open up new avenues to assemble unique N-heterocycle frameworks. Furthermore, the synthetic value of this protocol is demonstrated in the late-stage modification of physiologically active molecules and in the construction of aggregation-induced emission compounds.