Rapid Access to Fused Tetracyclic N-Heterocycles via Amino-to-Alkyl 1,5-Palladium Migration Coupled with Intramolecular C(sp(3))-C(sp(2)) Coupling

An unprecedented route for the preparation of fused tetracyclicN-heterocycles is presented through the palladium-catalyzed cyclizationof isocyanides with alkyne-tethered aryl iodides. In this transformation,a novel amino-to-alkyl 1,5-palladium migration/intramolecular C(sp(3))-C(sp(2)) coupling sequence was observedfirst. More importantly, isocyanide exhibited three roles, servingsimultaneously as a C1 synthon, a C1N1 synthon, and the donor of C(sp(3)) for C(sp(3))-C(sp(2)) coupling,and the reaction was the sole successful example that achieved C(sp(3))-H activation of isocyanide.

Automated summary

A novel method for the synthesis of fused tetracyclic N-heterocycles is described using palladium-catalyzed cyclization of isocyanides with alkyne-tethered aryl iodides. The reaction involves a unique amino-to-alkyl 1,5-palladium migration/intramolecular C(sp(3))-C(sp(2)) coupling sequence. Isocyanide plays multiple roles in this transformation, serving as a C1 synthon, a C1N1 synthon, and the donor of C(sp(3)) for C(sp(3))-C(sp(2)) coupling, and it represents the only successful example of C(sp(3))-H activation of isocyanide.