Aromatic Substitution by the S_RN1 Reaction

Abstract

The S RN 1 (Unimolecular Radical Nucleophilic Substitution) is a process through which nucleophilic substitution is achieved on aromatic and aliphatic compounds that do not react or react slowly through polar nucleophilic mechanisms. This transformation takes place through electron transfer steps with radicals and radical anions as intermediates. The S RN 1 mechanism was proposed for the first time in 1966 for the substitution of alkyl halides with electron‐withdrawing groups and in 1970 for the substitution of unactivated aryl halides. Since then, the scope of the process has increased considerably, and it constitutes an important synthetic method for achieving the substitution of unactivated aromatic and heteroaromatic substrates, vinyl halides, perfluoroalkyl iodides, and activated and non‐activated alkyl compounds. Nucleophiles that can be used include anions derived from carbon or heteroatoms, which react to form a new carbon‐carbon or carbon‐heteroatom bond. Several reviews have been published in relation to activated and non‐activated aliphatic S RN 1 reactions, to aromatic photoinitiated reactions, to S RN 1 reactions at aromatic centers, to reactions performed with electrochemical techniques, and to the synthetic applications of the process. This chapter attempts to cover aromatic S RN 1 reactions including all the relevant literature up to the end of 1996.

Organokatalyse und C‐H‐Aktivierung treffen auf Radikal‐ und Elektronentransferreaktionen

“…[34][35][36] Elektronentransferreaktionen des in Schema 4 vorschlagenen Typs -von einem stabilisierten Radikalanion auf ein Halogenid -sind auf dem Gebiet der S RN 1-Reaktionen mit Arylhalogeniden etabliert. [37,38] Vor diesem Hintergrund berichteten Kwong, Lei et al über interessante Befunde bei der Anwendung des von Bunnett und Creary eingeführten Dihalogenidtests, [39] der zur Untersuchung von Radikalanionenmechanismen dient. So lieferte die Reaktion der 1,4-Halogeniodbenzolderivate 9 a-c mit Benzol direkt das doppelt substituierte Produkt 11 (para-Terphenylen).…”

“…In der Tat ist die Kombination von KOtBu und Belichtung (als "entrainment" bezeichnet) eine der gängigsten Methoden zur Initiierung von S RN 1-Reaktionen. [37,38] Selbst ein Hydroxid kann unter Phasentransfer-Bedingungen als Reduktionsmittel (über ET) in Radikalkettenreaktionen wirken. [40] [41] die Radikalvorstufen und die Akzeptoren leicht variieren.…”

One‐Pot Synthesis of 3‐Substituted Isoquinolin‐1‐(2H)‐ones and Fused Isoquinolin‐1‐(2H)‐ones by SRN1 Reactions in DMSO

“…This mechanism is an important route to achieve the formation of a new C-C bond by the reaction of aromatic substrates with carbanions. [16] Scheme 1.…”

“…However, other reagents to initiate the reactions, such as Fe 2+ , SmI 2 , or Na(Hg) are also known. [16] In the propagation steps, the radical anion fragments into a radical and the anion of the leaving group [Equation (2)]. The radical reacts with the nucleophile to form the radical anion of the substitution product [Equation (3)].…”

SRN1 and Stille Reactions: A New Synthetic Strategy

“…The radical nucleophilic substitution, or S RN 1 reaction, is a process through which a nucleophilic substitution is obtained [1]. The scope of the process has considerably increased and nowadays it is an important synthetic possibility to achieve substitution of different substrates.…”