# Novel Strategies and Reagents for Introduction of Fluorinated Groups

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $392,558

## Abstract

Project Summary/Abstract
 Fluorine-containing molecules have desirable chemical, structural, pharmacological and biological
properties and have made a fundamental paradigm shift in pharmaceutical, agrochemical, and materials
science research over the last few decades. Notably, approximately 25% of marketed drugs and three out of the
ten top-selling pharmaceuticals in 2011 as well as one-third of the top-performing drugs contain at least one
fluorine atom in their structure. However, facile introduction of fluorine atom or fluorinated groups, especially
trifluoromethoxy (OCF3), polyfluoroalkoxy (ORf) and pentafluorosulfanyl (SF5) groups, into organic molecules
is recognized as a formidable challenge in synthetic chemistry. Most of the current methodologies either suffer
from poor substrate scope or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents.
Therefore, there is a significant gap between the needs of the chemical and pharmaceutical industry and the
efficiency of current strategies for installation of fluorinated groups into molecules of interest. Our long-term
goal is to bridge the gap by inventing bench-stable and easy-to-handle reagents and establishing operationally
simple, and scalable reactions to facilitate direct incorporation of the fluorinated groups into complex
molecules.
 In the proposed funding period, we will develop a general intramolecular polyfluoroalkoxylation (ORf)
reactions of arenes and heteroarenes. Due to their ubiquity in biologically active natural products,
pharmaceuticals, and agrochemicals, arenes and heteroarenes bearing ORf groups (e.g. OCF3, OCF2H, and
OCF2CF3) will serve as invaluable building blocks for all molecular screenings from medicinal chemistry to
materials science. In addition, we will invent novel reagents and reactions for late-stage radical
trifluoromethoxylation (OCF3) and pentafluorosulfanylation (SF5) of complex pharmaceuticals and natural
products, which will allow rapid biological-activity assays of trifluoromethoxylated and pentafluorosulfanylated
analogues. These reagents and synthetic methods could maximize structural diversity and provide insights for
future rational property design. To complement these diversity-oriented synthetic approaches, we will also
establish transition metal-catalyzed polyfluoroalkylation of phenols to achieve site-selective synthesis of
polyfluoroalkoxylated compounds. Given that the fluorinated groups exhibit favorable properties for biological
applications, our research program will allow access to and study of new fluorinated functional molecules to aid
the discovery and development of new drugs, biocompatible materials, bioprobes, and imaging agents.

## Key facts

- **NIH application ID:** 9934241
- **Project number:** 5R35GM119652-05
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Ming-Yu Ngai
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,558
- **Award type:** 5
- **Project period:** 2016-08-05 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934241

## Citation

> US National Institutes of Health, RePORTER application 9934241, Novel Strategies and Reagents for Introduction of Fluorinated Groups (5R35GM119652-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934241. Licensed CC0.

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