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

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2017 Jul 1

PMID 28665619

Citations 28

Authors

Matthew S McCammant

Stephen Thompson

Allen F Brooks

Shane W Krska

Peter J H Scott

Melanie S Sanford

Affiliations

Soon will be listed here.

Abstract

This communication describes a method for the nucleophilic radiofluorination of electron-rich arenes. The reaction involves the initial C(sp)-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 [F]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. The radiofluorination has been automated to access a 41 mCi dose of an F-labeled nimesulide derivative in high (2800 ± 700 Ci/mmol) specific activity.

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