# Copper as a Photocatalyst: Applications in Decarboxylative Fluorination

> **NIH NIH F32** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $22,702

## Abstract

PROJECT SUMMARY
 Fluorination of pharmaceutical compounds has been shown to increase their potency through 
modulation of their lipophilicity, acidity, and conformational bias. Photoredox decarboxylative 
fluorination in particular has been recognized as a powerful strategy for accessing fluorinated
compounds. However, these methods have typically been limited to cooperative catalysis with 
expensive Ir or organic photocatalysts. The Yoon lab has recently demonstrated a novel way to promote 
oxidative photochemical decarboxylation using simple CuII salts. Irradiation of the CuII carboxylate 
results in ligand-to-metal charge transfer, which leads to rapid decarboxylation to generate the alkyl 
radical. They applied this strategy towards the decarboxylative amination of benzylic carboxylic acids.
 This proposal details the application of this strategy towards oxidative decarboxylative fluorination 
and investigation of the reaction mechanism of this approach. In the first Aim, the photochemical 
oxidative decarboxylative fluorination of alkyl carboxylic acids will be developed using stoichiometric 
copper as both the terminal oxidant and decarboxylating agent. Both radical abstraction and 
nucleophilic fluorination mechanisms will be probed. The second Aim focuses on the development of a 
copper-catalyzed photochemical decarboxylative fluorination using Selectfluor as a source of fluorine 
and as an oxidant to turn over the catalyst. Use of catalytic copper allows for tuning of light absorption 
and copper complexation through ligand choice. UV-Vis will be used to identify ligands that form copper 
complexes that absorb light in the visible region and are stable in the presence of excess carboxylate. 
The reaction mechanism will be interrogated through quantum yield studies. Finally, upon development 
of the stoichiometric and catalytic methods, the mechanism and identity of the active copper species in 
solution will be investigated through UV-Vis, EPR, and computational studies as part of the third Aim.
 Development of this strategy provides a complementary approach to existing methods for the 
incorporation of fluorine in small molecules using simple, inexpensive reagents and affords mechanistic 
insight into a novel method for photochemical oxidative decarboxylation.

## Key facts

- **NIH application ID:** 10767327
- **Project number:** 5F32GM145089-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Caitlin Rebecca Lacker
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $22,702
- **Award type:** 5
- **Project period:** 2022-02-15 → 2024-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767327

## Citation

> US National Institutes of Health, RePORTER application 10767327, Copper as a Photocatalyst: Applications in Decarboxylative Fluorination (5F32GM145089-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10767327. Licensed CC0.

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