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1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls

Yuqiang Zhou, Kui-Cheng He, Weihao Zheng, Jingfang Lv, Shi-Mei He, Ning Yu, Yunbo Yang, Lv-Yan Liu, Kun Jiang, Ye Wei

2024Chemical Science19 citationsDOIOpen Access PDF

Abstract

generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (β-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Topics & Concepts

AnnulationPyridineHydrogen atomRelayAxial symmetryChemistryCombinatorial chemistryHydrogenStereochemistryPhotochemistryMedicinal chemistryOrganic chemistryPhysicsCatalysisQuantum mechanicsGroup (periodic table)Power (physics)Axial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralityAlkaloids: synthesis and pharmacology