Effect of solvent on radical cyclisation pathways: SRN1 vs. aryl-aryl bond forming mechanisms

Katie J. Emery, John A. Murphy, Tell Tuttle

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A recent paper identified a series of alternative cyclisation pathways of aryl radicals that resulted from electron transfer to various tethered haloarene–acetylarene substrates, in either benzene or DMSO as solvent. The electron transfer occurred from one of two enolates that were formed in the presence of KOtBu: either the enolate of the acetylarene, within the haloarene–acetylarene substrate, or the enolate 7 of the N,N’-dipropyl diketopiperazine (DKP) additive 6. This paper uses contemporary computational methods to determine the reaction pathways involved; depending on the substrate, the aryl radical underwent (i) SRN1 onto the enolate anion of the acetylarene, (ii) aryl-aryl bond formation, (iii) tandem hydrogen atom abstraction followed by SRN1 cyclisation and even (iv) ArC-N cleavage. The influence of the solvent was investigated. In this paper it is shown that the solvent influences which reactive species are present in the reaction mixture, and whether each species acts as an electron donor or an electron acceptor in the radical initiation or propagation steps. The main initiation step is a single electron transfer from the enolate anion 7 of the DKP additive in benzene, but in DMSO the initiation can occur from the enolate anion of the substrate itself. Using computational techniques a deeper understanding of the radical pathways involved has been obtained, which shows how we can use solvent to preferentially access products arising from either SRN1 or aryl-aryl bond formation pathways.
LanguageEnglish
Pages920-927
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume15
Issue number4
Early online date23 Dec 2016
DOIs
Publication statusPublished - 28 Jan 2017

Fingerprint

Cyclization
Electrons
electron transfer
Diketopiperazines
Anions
anions
Substrates
Dimethyl Sulfoxide
Benzene
benzene
cleavage
hydrogen atoms
Computational methods
electrons
Hydrogen
propagation
products
Atoms

Keywords

  • cyclisation
  • aryl-aryl bond forming
  • aryl radicals
  • tethered haloarene–acetylarene substrates
  • electron transfer
  • organic synthesis
  • radical chemistry

Cite this

@article{ee5cebbc28204386a42bb4626250b9b2,
title = "Effect of solvent on radical cyclisation pathways: SRN1 vs. aryl-aryl bond forming mechanisms",
abstract = "A recent paper identified a series of alternative cyclisation pathways of aryl radicals that resulted from electron transfer to various tethered haloarene–acetylarene substrates, in either benzene or DMSO as solvent. The electron transfer occurred from one of two enolates that were formed in the presence of KOtBu: either the enolate of the acetylarene, within the haloarene–acetylarene substrate, or the enolate 7 of the N,N’-dipropyl diketopiperazine (DKP) additive 6. This paper uses contemporary computational methods to determine the reaction pathways involved; depending on the substrate, the aryl radical underwent (i) SRN1 onto the enolate anion of the acetylarene, (ii) aryl-aryl bond formation, (iii) tandem hydrogen atom abstraction followed by SRN1 cyclisation and even (iv) ArC-N cleavage. The influence of the solvent was investigated. In this paper it is shown that the solvent influences which reactive species are present in the reaction mixture, and whether each species acts as an electron donor or an electron acceptor in the radical initiation or propagation steps. The main initiation step is a single electron transfer from the enolate anion 7 of the DKP additive in benzene, but in DMSO the initiation can occur from the enolate anion of the substrate itself. Using computational techniques a deeper understanding of the radical pathways involved has been obtained, which shows how we can use solvent to preferentially access products arising from either SRN1 or aryl-aryl bond formation pathways.",
keywords = "cyclisation, aryl-aryl bond forming, aryl radicals, tethered haloarene–acetylarene substrates, electron transfer, organic synthesis, radical chemistry",
author = "Emery, {Katie J.} and Murphy, {John A.} and Tell Tuttle",
year = "2017",
month = "1",
day = "28",
doi = "10.1039/c6ob02684b",
language = "English",
volume = "15",
pages = "920--927",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
number = "4",

}

Effect of solvent on radical cyclisation pathways : SRN1 vs. aryl-aryl bond forming mechanisms. / Emery, Katie J.; Murphy, John A.; Tuttle, Tell.

In: Organic and Biomolecular Chemistry, Vol. 15, No. 4, 28.01.2017, p. 920-927.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of solvent on radical cyclisation pathways

T2 - Organic and Biomolecular Chemistry

AU - Emery, Katie J.

AU - Murphy, John A.

AU - Tuttle, Tell

PY - 2017/1/28

Y1 - 2017/1/28

N2 - A recent paper identified a series of alternative cyclisation pathways of aryl radicals that resulted from electron transfer to various tethered haloarene–acetylarene substrates, in either benzene or DMSO as solvent. The electron transfer occurred from one of two enolates that were formed in the presence of KOtBu: either the enolate of the acetylarene, within the haloarene–acetylarene substrate, or the enolate 7 of the N,N’-dipropyl diketopiperazine (DKP) additive 6. This paper uses contemporary computational methods to determine the reaction pathways involved; depending on the substrate, the aryl radical underwent (i) SRN1 onto the enolate anion of the acetylarene, (ii) aryl-aryl bond formation, (iii) tandem hydrogen atom abstraction followed by SRN1 cyclisation and even (iv) ArC-N cleavage. The influence of the solvent was investigated. In this paper it is shown that the solvent influences which reactive species are present in the reaction mixture, and whether each species acts as an electron donor or an electron acceptor in the radical initiation or propagation steps. The main initiation step is a single electron transfer from the enolate anion 7 of the DKP additive in benzene, but in DMSO the initiation can occur from the enolate anion of the substrate itself. Using computational techniques a deeper understanding of the radical pathways involved has been obtained, which shows how we can use solvent to preferentially access products arising from either SRN1 or aryl-aryl bond formation pathways.

AB - A recent paper identified a series of alternative cyclisation pathways of aryl radicals that resulted from electron transfer to various tethered haloarene–acetylarene substrates, in either benzene or DMSO as solvent. The electron transfer occurred from one of two enolates that were formed in the presence of KOtBu: either the enolate of the acetylarene, within the haloarene–acetylarene substrate, or the enolate 7 of the N,N’-dipropyl diketopiperazine (DKP) additive 6. This paper uses contemporary computational methods to determine the reaction pathways involved; depending on the substrate, the aryl radical underwent (i) SRN1 onto the enolate anion of the acetylarene, (ii) aryl-aryl bond formation, (iii) tandem hydrogen atom abstraction followed by SRN1 cyclisation and even (iv) ArC-N cleavage. The influence of the solvent was investigated. In this paper it is shown that the solvent influences which reactive species are present in the reaction mixture, and whether each species acts as an electron donor or an electron acceptor in the radical initiation or propagation steps. The main initiation step is a single electron transfer from the enolate anion 7 of the DKP additive in benzene, but in DMSO the initiation can occur from the enolate anion of the substrate itself. Using computational techniques a deeper understanding of the radical pathways involved has been obtained, which shows how we can use solvent to preferentially access products arising from either SRN1 or aryl-aryl bond formation pathways.

KW - cyclisation

KW - aryl-aryl bond forming

KW - aryl radicals

KW - tethered haloarene–acetylarene substrates

KW - electron transfer

KW - organic synthesis

KW - radical chemistry

UR - http://www.scopus.com/inward/record.url?scp=85010644675&partnerID=8YFLogxK

U2 - 10.1039/c6ob02684b

DO - 10.1039/c6ob02684b

M3 - Article

VL - 15

SP - 920

EP - 927

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 4

ER -