# Copper Catalyzed Fluorination of Aryl Halides

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $66,390

## Abstract

Project Summary.
 The aryl fluoride motif is prevalent in a range of important compounds. >25% of agrochemicals and
>20% of pharmaceuticals contain fluorine, often in the form of aryl fluoride. Additionally, 18F is the favored
radioisotope in Positron Emission Tomography (PET), an in-vivo imaging technique used in the diagnosis and
treatment of diseases such as Alzheimer's and Parkinson's. Despite the widespread use of aryl fluorides in
these areas, there are currently very few robust and functional group tolerant methods for their synthesis.
Developing more efficient methods to introduce fluorine into organic molecules is therefore a priority. One
promising method is the transition metal catalyzed synthesis of aryl fluorides from readily available aryl halides.
However, there are few reported systems for this transformation. The two prior Cu-based systems use simple
Cu salts and pose significant drawbacks that need to be addressed, such as the requirement for high
temperatures, an excess of expensive fluoride source (AgF), supersoichiometric Cu, or limitation to specific
directing groups. Developing systems that overcome these limitations is therefore an extremely important
unsolved problem in the field. In order to improve on these systems, we aim to address key challenges
inherent to Cu: (i) the instability of most CuIF complexes to disproportionation to form inactive Cu0 and CuF2
and (ii) the difficulty of the oxidative addition step. To overcome these issues we will move from simple Cu salts
to well-defined copper complexes supported by N-heterocyclic carbenes (NHCs), cyclic alkyl amino carbene
(CAACs), or related ligands. We hypothesize that these ligands will stabilize CuI intermediates, as well as favor
oxidative addition, leading to more efficient catalysts. Specifically, we aim to use carbene-supported Cu
complexes to: (1) study the effects of ligand properties on stoichiometric fluorination of aryl halides, (2) develop
catalytic fluorination of a range of pharmaceutically relevant aryl halide scaffolds (3) synthesize 18F labeled
tracer molecules for use in PET imaging. Completion of these aims will result in improved systems for the
fluorination of aryl halides that can be applied to synthesis of pharmaceuticals, agrochemicals and PET tracers.
Preliminary results have been obtained that support the feasibility of each proposed aim.

## Key facts

- **NIH application ID:** 10115518
- **Project number:** 5F32GM136022-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Liam Shin Sharninghausen
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115518

## Citation

> US National Institutes of Health, RePORTER application 10115518, Copper Catalyzed Fluorination of Aryl Halides (5F32GM136022-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10115518. Licensed CC0.

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