# Asymmetric Catalysis and Selective C-F Bond Functionalization with Organofluorines

> **NIH NIH R15** · GEORGETOWN UNIVERSITY · 2023 · $458,705

## Abstract

PROJECT ABSTRACT
The ever-increasing demand for synthetic tools that expand currently available chemical space
and provide efficient access to new biologically active compounds has shifted significant attention
toward the development of methods that produce chemically versatile multifunctional fluorinated
chiral compounds or accomplish carbon-fluorine bond functionalization in new ways that remove
long-standing boundaries of traditional chemical synthesis. Despite considerable progress, in
particular with hydrodefluorinations, these tasks remain quite difficult because the profound
electron-withdrawing and stereoelectronic effects of fluorine often interfere with established
synthetic protocols and dramatically alter reaction outcomes compared to nonfluorinated analogs.
Given the abundance and diversity of readily available fluorinated building blocks that await
chemical modification, the introduction of methodologies that overcome these challenges are
expected to set the stage for new synthetic tools and possibilities that streamline or enable the
production of current and future drugs.
 The proposed research aims to introduce carbon-fluorine bond activation chemistry and
asymmetric methods that combine exceptional reaction control, scope and functional group
tolerance. The C-F bond, typically considered chemically inert, will become a strategically useful
entity that can be selectively activated under mild reaction conditions which will open the door to
a variety of unprecedented applications including late-stage functionalization and stereoselective
carbon-carbon bond formation. In addition, (organo)catalytic asymmetric methods that efficiently
produce fluorinated structures exhibiting one or two elements of chirality, a wide range of
functional groups, and pharmaceutically relevant motifs will be introduced. These efforts will afford
a diverse pool of synthetically versatile structures with broad utility and respond to the rapidly
increasing demand for high-yielding stereodivergent and atroposelective procedures among the
synthetic and medicinal chemistry communities.
 While emphasis lies on the introduction of new synthetic methodologies and asymmetric
catalysis development, the mechanistic underpinnings will be fully explored to guide optimization
efforts and to stimulate similar efforts and discoveries in other research groups. The general
feasibility and the corresponding prospects are supported by ample proof-of-concept results that
show how organofluorines can be prepared and utilized in currently not possible ways. Finally,
the suitability of the proposed transformations for the synthesis of biologically active compounds
will be demonstrated.

## Key facts

- **NIH application ID:** 10729601
- **Project number:** 2R15GM106260-04
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Christian Wolf
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $458,705
- **Award type:** 2
- **Project period:** 2013-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10729601

## Citation

> US National Institutes of Health, RePORTER application 10729601, Asymmetric Catalysis and Selective C-F Bond Functionalization with Organofluorines (2R15GM106260-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10729601. Licensed CC0.

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