Rapid Access to Fused Tetracyclic N-Heterocycles via Amino-to-Alkyl 1,5-Palladium Migration Coupled with Intramolecular C(sp³)–C(sp²) Coupling

Abstract

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.

Taming the Selective C−H Bond Activation through 1,5‐Palladium Migration

“…Recently, Chen and Shan demonstrated an unprecedented cascade cyclization of isocyanides 69 with alkyne-tethered aryl iodides 70, in which an amino-to-alkyl 1,5-palladium migration was described for the first time. [26] A range of fused tetracyclic N-heterocyclic product 71 could be prepared up to 86 % yield (Scheme 17a). Similar to previous studies, the authors also perform deuterium-labelled experiment.…”

Electrophile-Controlled Regiodivergent Palladium-Catalyzed Imidoylative Spirocyclization of Cyclic Alkenes

“…In the past decades, Pd-catalyzed isocyanide insertion reactions have witnessed rapid development . In this aspect, a strategy of functionalized isocyanide was successfully developed and applied for the construction of a variety of N -heterocycles .…”