A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study

Shelli A. Miller; Bas van Beek; Trevor A. Hamlin; F. Matthias Bickelhaupt; Nicholas E. Leadbeater

doi:10.1016/j.jfluchem.2018.08.005

A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study

Shelli A. Miller
, Bas van Beek
, Trevor A. Hamlin^*
, F. Matthias Bickelhaupt
, Nicholas E. Leadbeater

^*Corresponding author for this work

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Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfinate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.

Original language	English
Pages (from-to)	94-100
Number of pages	7
Journal	Journal of Fluorine Chemistry
Volume	214
Early online date	11 Aug 2018
DOIs	https://doi.org/10.1016/j.jfluchem.2018.08.005
Publication status	Published - Oct 2018

Funding

This work was supported financially by the University of Connecticut . Additionally, we thank the Netherlands Organization for Scientific Research (NWO) for financial support through the Planetary and Exo-Planetary Science program (PEPSci) and the Dutch Astrochemistry Network (DAN). We would also like to thank undergraduate students Joshua Paolillo and Madeline Williams (University of Connecticut) for contributions to the experimental components of this project.

Funders
Dutch Astrochemistry Network
Planetary and Exo-Planetary Science program
University of Connecticut
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 6 Clean Water and Sanitation

Keywords

Density functional calculations
Indoles
Langlois reagent
Photocatalysis
Trifluoromethylation

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10.1016/j.jfluchem.2018.08.005

A methodology for the photocatalyzed radical trifluoromethylation of indolesFinal published version, 923 KBLicence: Article 25fa Dutch Copyright Act

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title = "A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study",

abstract = "A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfinate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.",

keywords = "Density functional calculations, Indoles, Langlois reagent, Photocatalysis, Trifluoromethylation",

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T2 - A combined experimental and computational study

AU - Miller, Shelli A.

AU - van Beek, Bas

AU - Hamlin, Trevor A.

AU - Bickelhaupt, F. Matthias

AU - Leadbeater, Nicholas E.

PY - 2018/10

Y1 - 2018/10

N2 - A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfinate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.

AB - A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfinate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.

KW - Density functional calculations

KW - Indoles

KW - Langlois reagent

KW - Photocatalysis

KW - Trifluoromethylation

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VL - 214

SP - 94

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JO - Journal of Fluorine Chemistry

JF - Journal of Fluorine Chemistry

ER -

A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study

Abstract

Funding

UN SDGs

Keywords

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