An unprecedented route for the preparation of fused tetracyclic N-heterocycles is presented through the palladium-catalyzed cyclization of isocyanides with alkyne-tethered aryl iodides. In this transformation, a novel amino-to-alkyl 1,5-palladium migration/intramolecular C(sp3)-C(sp2) coupling sequence was observed first. More importantly, isocyanide exhibited three roles, serving simultaneously as a C1 synthon, a C1N1 synthon, and the donor of C(sp3) for C(sp3)-C(sp2) coupling, and the reaction was the sole successful example that achieved C(sp3)-H activation of isocyanide.