Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

Jeroen B.I. Sap; Natan J.W. Straathof; Thomas Knauber; Claudio F. Meyer; Maurice Médebielle; Laura Buglioni; Christophe Genicot; Andrés A. Trabanco; Timothy Noël; Christopher W. Am Ende; Véronique Gouverneur

doi:10.1021/jacs.0c03881

Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

Jeroen B.I. Sap
, Natan J.W. Straathof
, Thomas Knauber
, Claudio F. Meyer
, Maurice Médebielle
, Laura Buglioni
, Christophe Genicot
, Andrés A. Trabanco
, Timothy Noël
, Christopher W. Am Ende
, Véronique Gouverneur (Corresponding author)

Micro Flow Chemistry and Synthetic Methodology

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

152 Citations (Scopus)

Abstract

Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.

Original language	English
Pages (from-to)	9181-9187
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	142
Issue number	20
DOIs	https://doi.org/10.1021/jacs.0c03881
Publication status	Published - 20 May 2020

Funding

This project has received funding from the Engineering and Physical Sciences Research Council (EP/N509711/1) (J.B.I.S.), European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie Grant Agreement 721902 (C.F.M.) and 840724 (L.B.). Gloria Rosetto (Williams group, Oxford) and Gabriele Laudadio (Eindhoven) are acknowledged for assistance with the deuteration and cyclic voltammetry experiments, respectively.

Funders	Funder number
European Union's Horizon 2020 - Research and Innovation Framework Programme	721902, 840724
Engineering and Physical Sciences Research Council	EP/N509711/1

Access to Document

10.1021/jacs.0c03881

Cite this

Sap, J. B. I., Straathof, N. J. W., Knauber, T., Meyer, C. F., Médebielle, M., Buglioni, L., Genicot, C., Trabanco, A. A., Noël, T., Am Ende, C. W., & Gouverneur, V. (2020). Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery. Journal of the American Chemical Society, 142(20), 9181-9187. https://doi.org/10.1021/jacs.0c03881

@article{ea3b29905e674385899bb4f4c949fa14,

title = "Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery",

abstract = "Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene. ",

author = "Sap, \{Jeroen B.I.\} and Straathof, \{Natan J.W.\} and Thomas Knauber and Meyer, \{Claudio F.\} and Maurice M{\'e}debielle and Laura Buglioni and Christophe Genicot and Trabanco, \{Andr{\'e}s A.\} and Timothy No{\"e}l and \{Am Ende\}, \{Christopher W.\} and V{\'e}ronique Gouverneur",

year = "2020",

month = may,

day = "20",

doi = "10.1021/jacs.0c03881",

language = "English",

volume = "142",

pages = "9181--9187",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "20",

}

Sap, JBI, Straathof, NJW, Knauber, T, Meyer, CF, Médebielle, M, Buglioni, L, Genicot, C, Trabanco, AA, Noël, T, Am Ende, CW & Gouverneur, V 2020, 'Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery', Journal of the American Chemical Society, vol. 142, no. 20, pp. 9181-9187. https://doi.org/10.1021/jacs.0c03881

TY - JOUR

T1 - Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

AU - Sap, Jeroen B.I.

AU - Straathof, Natan J.W.

AU - Knauber, Thomas

AU - Meyer, Claudio F.

AU - Médebielle, Maurice

AU - Buglioni, Laura

AU - Genicot, Christophe

AU - Trabanco, Andrés A.

AU - Noël, Timothy

AU - Am Ende, Christopher W.

AU - Gouverneur, Véronique

PY - 2020/5/20

Y1 - 2020/5/20

N2 - Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.

AB - Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.

UR - https://www.scopus.com/pages/publications/85087525263

U2 - 10.1021/jacs.0c03881

DO - 10.1021/jacs.0c03881

M3 - Article

C2 - 32379965

AN - SCOPUS:85087525263

SN - 0002-7863

VL - 142

SP - 9181

EP - 9187

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 20

ER -

Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this