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Title: Cu-mediated C–H 18F-fluorination of electron-rich (hetero)arenes

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 [1] ; ORCiD logo [1] ;  [2] ; ORCiD logo [1] ; ORCiD logo [1]
  1. Univ. of Michigan, Ann Arbor, MI (United States)
  2. Merck Sharp &, Dohme, Kenilworth, NJ (United States)
Publication Date:
Grant/Contract Number:
SC0012484
Type:
Published Article
Journal Name:
Organic Letters
Additional Journal Information:
Journal Volume: 19; Journal Issue: 14; Journal ID: ISSN 1523-7060
Publisher:
American Chemical Society
Research Org:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1367716
Alternate Identifier(s):
OSTI ID: 1372897

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., 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.. 2017. "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 = 14,
volume = 19,
place = {United States},
year = {2017},
month = {6}
}