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

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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
DOIs	https://doi.org/10.1016/j.jfluchem.2018.08.005
Publication status	Published - Oct 2018
Externally published	Yes

Keywords

Density functional calculations
Indoles
Langlois reagent
Photocatalysis
Trifluoromethylation

ASJC Scopus subject areas

Biochemistry
Environmental Chemistry
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.1016/j.jfluchem.2018.08.005

Cite this

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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",

author = "Miller, \{Shelli A.\} and \{van Beek\}, Bas and Hamlin, \{Trevor A.\} and Bickelhaupt, \{F. Matthias\} and Leadbeater, \{Nicholas E.\}",

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year = "2018",

month = oct,

doi = "10.1016/j.jfluchem.2018.08.005",

language = "English",

volume = "214",

pages = "94--100",

journal = "Journal of Fluorine Chemistry",

issn = "0022-1139",

publisher = "Elsevier B.V.",

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T1 - A methodology for the photocatalyzed radical trifluoromethylation of indoles

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

UR - https://www.scopus.com/pages/publications/85051994862

U2 - 10.1016/j.jfluchem.2018.08.005

DO - 10.1016/j.jfluchem.2018.08.005

M3 - Article

AN - SCOPUS:85051994862

SN - 0022-1139

VL - 214

SP - 94

EP - 100

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

Keywords

ASJC Scopus subject areas

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