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

• Published in: Chemical science (Cambridge) 2024-05, Vol.15 (2), p.752-7514
• Main Authors: Zhou, Yu-Qiang, He, Kui-Cheng, Zheng, Wei-Hao, Lv, Jing-Fang, He, Shi-Mei, Yu, Ning, Yang, Yun-Bo, Liu, Lv-Yan, Jiang, Kun, Wei, Ye
• Format: Article
• Language: English
• Subjects: Cations; Chemical reactions; Chemical synthesis; Chemistry; Cleavage; Functional groups; Functional materials; Hydrogen atoms; Organic chemistry; Pyridines; Radicals; Reaction products; Relay
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d4sc01858c

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,β-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ 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. A new 1,5-hydrogen atom transfer mode of α-iminyl radical cations has been explored, which enables the efficient construction of fused pyridine and axially chiral heterobiaryl scaffolds via relay annulations.