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Title: Cu-Mediated C$-$H 18F-Fluorination of Electron-Rich (Hetero)arenes

Abstract

This communication describes a method for the nucleophilic radiofluorination of electron-rich arenes. The reaction involves the initial C(sp 2)–H functionalization of an electron-rich arene with MesI(OH)OTs to form a (mesityl)(aryl)iodonium salt. This salt is then used in situ in a Cu-mediated radiofluorination with [ 18F]KF. This approach leverages the stability and availability of electron-rich arene starting materials to enable mild late-stage radiofluorination of toluene, anisole, aniline, pyrrole, and thiophene derivatives. Finally, the radiofluorination has been automated to access a 41 mCi dose of an 18F-labeled nimesulide derivative in high (2800 ± 700 Ci/mmol) specific activity.

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [2];  [3]; ORCiD logo [2]; ORCiD logo [1]
  1. Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
  2. Department of Radiology, University of Michigan, 1301 Catherine, Ann Arbor, Michigan 48109, United States
  3. Chemistry Capabilities and Screening, Merck Sharp &, Dohme, Kenilworth, New Jersey 07033, United States
Publication Date:
Research Org.:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1367716
Alternate Identifier(s):
OSTI ID: 1372897
Grant/Contract Number:  
SC0012484
Resource Type:
Published Article
Journal Name:
Organic Letters
Additional Journal Information:
Journal Name: Organic Letters; Journal ID: ISSN 1523-7060
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

McCammant, Matthew S., Thompson, Stephen, Brooks, Allen F., Krska, Shane W., Scott, Peter J. H., and Sanford, Melanie S. Cu-Mediated C$-$H 18F-Fluorination of Electron-Rich (Hetero)arenes. United States: N. p., 2017. Web. doi:10.1021/acs.orglett.7b01902.
McCammant, Matthew S., Thompson, Stephen, Brooks, Allen F., Krska, Shane W., Scott, Peter J. H., & Sanford, Melanie S. Cu-Mediated C$-$H 18F-Fluorination of Electron-Rich (Hetero)arenes. United States. doi:10.1021/acs.orglett.7b01902.
McCammant, Matthew S., Thompson, Stephen, Brooks, Allen F., Krska, Shane W., Scott, Peter J. H., and Sanford, Melanie S. Fri . "Cu-Mediated C$-$H 18F-Fluorination of Electron-Rich (Hetero)arenes". United States. doi:10.1021/acs.orglett.7b01902.
@article{osti_1367716,
title = {Cu-Mediated C$-$H 18F-Fluorination of Electron-Rich (Hetero)arenes},
author = {McCammant, Matthew S. and Thompson, Stephen and Brooks, Allen F. and Krska, Shane W. and Scott, Peter J. H. and Sanford, Melanie S.},
abstractNote = {This communication describes a method for the nucleophilic radiofluorination of electron-rich arenes. The reaction involves the initial C(sp2)–H functionalization of an electron-rich arene with MesI(OH)OTs to form a (mesityl)(aryl)iodonium salt. This salt is then used in situ in a Cu-mediated radiofluorination with [18F]KF. This approach leverages the stability and availability of electron-rich arene starting materials to enable mild late-stage radiofluorination of toluene, anisole, aniline, pyrrole, and thiophene derivatives. Finally, the radiofluorination has been automated to access a 41 mCi dose of an 18F-labeled nimesulide derivative in high (2800 ± 700 Ci/mmol) specific activity.},
doi = {10.1021/acs.orglett.7b01902},
journal = {Organic Letters},
number = ,
volume = ,
place = {United States},
year = {2017},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1021/acs.orglett.7b01902

Citation Metrics:
Cited by: 12 works
Citation information provided by
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Works referencing / citing this record:

[Rh III (Cp*)]-catalyzed arylfluorination of α-diazoketoesters for facile synthesis of α-aryl-α-fluoroketoesters
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  • Organic & Biomolecular Chemistry, Vol. 17, Issue 5
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Hypervalent aryliodine compounds as precursors for radiofluorination
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  • Pike, Victor W.
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Automated synthesis of PET radiotracers by copper-mediated 18 F-fluorination of organoborons: Importance of the order of addition and competing protodeborylation
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  • Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 61, Issue 3
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[Rh III (Cp*)]-catalyzed arylfluorination of α-diazoketoesters for facile synthesis of α-aryl-α-fluoroketoesters
journal, January 2019

  • Ng, Fo-Ning; Chan, Chun-Ming; Li, Jianbin
  • Organic & Biomolecular Chemistry, Vol. 17, Issue 5
  • DOI: 10.1039/c8ob02801j