# Methods for the Functionalization of C-H Bonds

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $292,450

## Abstract

Project Abstract
Due to the unique physicochemical properties of fluorinated small molecules, fluorides stand as one of the
simplest and sought after functional groups in medicinal chemistry. For example, the inclusion of fluorine in
biologically active molecules increases the lipophilicity, bioavailability, and oxidative stability. This allows
medicinal chemists to tune the metabolic stability and biodistribution of lead compounds. The primary goal of
the proposed research is to develop directed H-atom abstraction as a versatile C–H fluorination strategy for
synthesis. While extensive methodology has been developed for the functionalization of Csp2–H bonds, Csp3–
H bonds remain challenging. The common approach of using noble metals for C–H activation is currently
limited to only a few “privileged” directing groups that function under specialized conditions. The chemistry
proposed here employs directed H-atom transfer to easily access Csp3–H bonds. The reactions arising from
the proposed chemistry will complement and expand current C–H activation strategies through broadened
directing-group compatibility and targetable Csp3–H bonds. In this project, iron-catalyzed reactions will allow a
range of directing groups to selectively fluorinate specific Csp3–H bonds in a molecule. This paradigm will be
employed in the fluorination of activated (Aim 1) and unactivated (Aim 2) Csp3–H bonds using readily available
fluoride starting materials. These transformations will find application in the synthesis and derivatization of drug
candidates, natural products, and biological probes.

## Key facts

- **NIH application ID:** 10004676
- **Project number:** 5R01GM121668-05
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Silas P Cook
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $292,450
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004676

## Citation

> US National Institutes of Health, RePORTER application 10004676, Methods for the Functionalization of C-H Bonds (5R01GM121668-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10004676. Licensed CC0.

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