# Electrochemically Generated Hypervalent Iodoarenes: An Addressable and Sustainable Catalytic Platform for Difluorination and Trifluoromethylation

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $55,314

## Abstract

Project Abstract
The controlled introduction of fluorine into biologically relevant compounds helps prevent,
diagnose, and treat disease. The deployment of this element in drug design has been shown to
modulate key biochemical properties, such as metabolic stability, solubility, and activity. Among
the diverse-array of fluorinated building blocks, trifluoromethyl groups and vicinal difluorides
are targeted motifs due to their potential to serve as stable, non-toxic mimics of methyl groups or
to induce chiral bioisosteres, respectively. Therefore, the continued development of
methodologies that can access and manipulate both moieties are of synthetic and medicinal
value. To this end, hypervalent iodoarenes (I(III)Ar) have emerged as a promising, versatile, and
metal-free fluorinating and trifluoromethylating agent. However, their catalytic utilization
remains rare due to fundamental challenges associated with the rate and methods of their
regeneration, resulting in parasitic side reactions and limiting the substrate scope. In order to
selectively and controllably install difluorinated and trifluoromethylated motifs, a catalytic,
sustainable, and addressable system is required.
This proposal puts forth a new molecular electrocatalytic strategy to solve challenges of
selectivity and to install rare vicinal difluoride C-F bonds and O-CF3 bonds. Molecular
electrocatalysts are developed based on the known thermal chemistry of I(III)Ar. The molecular
electrocatalysts can be tailored, enabling the development of a new class of catalysts for
difluorination and trifluoromethylation. The electrochemical mechanism of I(III)Ar is inspired
by the analysis of existing electrochemical data on related compounds. Detailed studies of the
rate of electrocatalyst generation will provide insights into the mechanism of the organic
electrosynthesis strategy. The anticipated selectivity of the molecular electrocatalyst to a wide
array of differing substrates will also facilitate the controlled difluorination of electron-rich
substrates for the first time. In addition to enabling the synthesis of fluorinated and
trifluoromethylated compounds, these studies will provide a framework for the development of
other molecular electrocatalysts for further complex organic transformations.

## Key facts

- **NIH application ID:** 9989624
- **Project number:** 5F32GM130025-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Anna Wuttig
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $55,314
- **Award type:** 5
- **Project period:** 2018-08-27 → 2021-06-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989624

## Citation

> US National Institutes of Health, RePORTER application 9989624, Electrochemically Generated Hypervalent Iodoarenes: An Addressable and Sustainable Catalytic Platform for Difluorination and Trifluoromethylation (5F32GM130025-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9989624. Licensed CC0.

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