Recent progress in the generation and use of nitrogen-centred radicals

Abstract

Nitrogen-centred radicals hold much promise as useful synthetic intermediates. Even though their popularity is still extremely limited and very far from matching that of carbon radicals, the recent development of various routes allowing their generation under mild conditions and a better appreciation of their reactivity thanks to the increased availability of absolute rate constants should encourage their use. It is hoped that this tutorial review will help increase the awareness of synthetic chemists and help revive the interest in these forgotten species.

Visible‐Light‐Promoted Iminyl‐Radical Formation from Acyl Oximes: A Unified Approach to Pyridines, Quinolines, and Phenanthridines

“…[1] During the past few years, transition-metal catalysis has been demonstrated as a powerful tool for breaking the N À O bond of acyl oximes through oxidative addition of the metal to the NÀO bond and the subsequent formation of various multisubstituted heterocycles, such as pyridines, indoles, isoquinolines, and imidazoles (Scheme 1 a). [2] Another pathway for cleavage of the N À O bond is homolysis under microwave (> 160 8C) or UV irradiation.…”

“…[3] Furthermore, the NÀO bond of acyl oximes can also be cleaved to give iminyl radicals, as well as acyloxy anions, through single-electron reduction with the assistance of an oxidant owing to the weak bond energy and electronic properties of the N À O bond (Scheme 1 c). [1] Although iminyl radicals were considered to be formed by a Cu I /Cu II 1 e À transfer mechanism from acyl oximes in several coppercatalyzed reactions, [2g, 4] the oxidative addition of Cu I to NÀO bonds through a Cu I /Cu III cycle is an inevitable competitive pathway, especially at high temperature.…”

A Simple and Broadly Applicable C−N Bond Forming Dearomatization Protocol Enabled by Bifunctional Amino Reagents

“…Thus, the N−O bond acts as an internal oxidant only, and is not effective as an external oxidant. The conversion of 3 e′ to 4 e is not affected by addition of TEMPO or BHT, which suggests that potential radical‐based pathways involving initial N−O homolysis are not operative 16. Additionally, we examined the behavior of alkenyl systems 11 a and 11 b because N‐centered radicals are known to undergo fast 5‐ exo cyclization onto alkene acceptors (Scheme 2 B) 16, 17.…”

Synthesis of Arylamines via Aminium Radicals

“…As such, methods for the direct amination of unfunctionalized aromatic compounds are very desirable but far from being general. [6] Nitrogen radicals [7] are highly reactive species that are now witnessing aresurgence of synthetic interest owing to the ability of photoredox catalysis [8] to promote single-electron transfer (SET) [9] processes under mild conditions.…”

“…As such, methods for the direct amination of unfunctionalized aromatic compounds are very desirable but far from being general. [6] Nitrogen radicals [7] are highly reactive species that are now witnessing aresurgence of synthetic interest owing to the ability of photoredox catalysis [8] to promote single-electron transfer (SET) [9] processes under mild conditions.[10] While highly electrophilic amidyl [11] and sulfamidyl radicals [12] have been successfully coupled with highly electron-rich aromatic compounds (e.g.,i ndole,p yrrole), the use of dialkyl-substituted nitrogen radicals (aminyl radicals) in related arylations has yet to be described. This lack of synthetic application can be explained by the intrinsic nucleophilic nature of aminyls, which causes repulsive interactions between their lone pair and the aromatic ring.…”