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

McCammant, Matthew S.; Thompson, Stephen; Brooks, Allen F.; Krska, Shane W.; Scott, Peter J. H.; Sanford, Melanie S.

doi:10.1021/acs.orglett.7b01902

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

Journal Article · Fri Jun 30 00:00:00 EDT 2017 · Organic Letters

DOI:https://doi.org/10.1021/acs.orglett.7b01902· OSTI ID:1367716

McCammant, Matthew S. ^[1];

^[2];

^[2]; Krska, Shane W. ^[3];

^[2];

^[1]

Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
Department of Radiology, University of Michigan, 1301 Catherine, Ann Arbor, Michigan 48109, United States
Chemistry Capabilities and Screening, Merck Sharp &, Dohme, Kenilworth, New Jersey 07033, United States

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.

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Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0012484

OSTI ID:: 1367716

Alternate ID(s):: OSTI ID: 1372897

Journal Information:: Organic Letters, Journal Name: Organic Letters; ISSN 1523-7060

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 64 works

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