Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation

Abstract

Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay π-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative π-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C–H arylation.

Cyclic Homo- and Heterohalogen Di-λ3-diarylhalonium Structures

“…For example, while the archetypal five-membered structure type B (Figure ) is particularly stable toward conventional nucleophilic attack, this and the larger iodacycles (e . g., type C ) undergo all sorts of ring-opening and ring-enlargement reactions under metal-catalyzed , or single electron transfer (SET) conditions . Beyond this synthetic potential, cyclic diaryliodonium cations are also known to interfere with a variety of biological electron-transport systems.…”

Modular synthesis of C2-symmetric nitrogen-containing polyaromatics via visible light-enabled reductive aza-6π electrocyclization

“…For instance, Itami's group and other groups developed an aza-annulative π-extension (aza-APEX) strategy for one-pot construction of π-extended fused heteroarenes through direct C–H activation of small (hetero)aromatic templates. 4 Conversely, transition-metal-catalyzed inter- or intra-molecular cyclization of alkynes proved to be effective synthetic protocols for C 1 -symmetric N-PACs. 5 Moreover, similar transformations could be realized by electrochemical devices.…”