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

> **NIH NIH R15** · GEORGETOWN UNIVERSITY · 2020 · $422,066

## Abstract

PROJECT ABSTRACT
The ever-increasing demand for synthetic methods that expand currently accessible chemical
space and provide efficient access to biologically active compounds has begun to shift attention
toward the development of largely unexplored Csp3-F bond functionalization chemistry. Despite
considerable progress, in particular with hydrodefluorinations, this task remains quite challenging
because the profound electron-withdrawing and stereoelectronic effects of fluorine often interfere
with established synthetic protocols and dramatically alter reaction outcomes compared to
nonfluorinated analogues. Given the abundance and diversity of readily available fluorinated
compounds, the introduction of strategies that provide control over the unique stability and
reactivity patterns of the aliphatic carbon-fluorine bond are expected to set the stage for extremely
powerful synthetic venues that streamline the production of current and future drugs.
 The goals of the proposed research are to introduce new Csp3-F bond activation chemistry
that is complementary to existing methodologies by enabling unprecedented carbon-carbon and
carbon-heteroatom bond formation and an array of new synthetic opportunities with exceptional
reaction control, scope and functional group tolerance. The Csp3-F bond, typically considered
chemically inert, will become a strategically useful entity representing a latent carbon nucleophile
or electrophile, for example via unique Umpolung pathways that allow selective manipulation of
orthogonal reactivity modes, with multiple applications including late-stage functionalization. In
addition, the Csp3-F bond activation methodology will be extended to catalytic asymmetric cross-
coupling chemistry and the (organo)catalytic enantio- and diastereoselective synthesis of a variety
of multifunctional organofluorines carrying two contiguous chirality centers from the challenging
class of fluoronitriles will be pioneered.
 While emphasis lies on the development of new synthetic methodologies and asymmetric
catalysis, the usefulness of the proposed transformations and reaction products in the total
synthesis of biologically active compounds will also be explored. The general feasibility and the
synthetic prospects are highlighted with ample proof-of-concept results and mechanistic insights
that underscore the broad impact of asymmetric catalysis with fluoronitriles and of strikingly
diverse C-F bond functionalization pathways which altogether will exploit organofluorines in
currently not possible ways.

## Key facts

- **NIH application ID:** 10114436
- **Project number:** 2R15GM106260-03
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Christian Wolf
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,066
- **Award type:** 2
- **Project period:** 2013-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114436

## Citation

> US National Institutes of Health, RePORTER application 10114436, Selective C-F Bond Functionalization and Asymmetric Synthesis with Organofluorines (2R15GM106260-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114436. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*