# Designed Mediators for Selective Electrochemical C H Oxidation

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $64,926

## Abstract

PROJECT SUMMARY/ABSRTACT
 The primary goal of this research project will be the development of designed mediators for selective
electrochemical oxidation of sp3 C–H bonds, through the use of descriptive statistical modeling. Remote C–H oxidation
strategies are highly desirable from a synthetic standpoint and have implications for human health because of the potential
for late stage derivatization of drugs. However, remote C–H functionalization methodologies have been plagued with low
levels of selectivity, compared to the high levels of selectivity that have become the standard in modern organic synthesis.
To address this complex problem, an intensive study into the molecular properties which bring about selectivity for C–H
activation processes will be undertaken.
 Pyridine N-oxide and its derivatives will be evaluated as a new potential class of redox mediators (Aim 1). In order
to correlate structural and electronic properties of C–H oxidation mediators with selectivity, a library of PNO derivatives
will be synthesized and site-selectivity data (ΔΔG‡) will be collected using model substrates that have varying complexity.
Electrochemical oxidation of PNO derivatives would produce highly electrophilic radical intermediates capable of
abstracting electron rich sp3 C–H bonds. In the presence of molecular oxygen, a net C–H oxidation is expected. The PNO
scaffold provides the modularity required to build a large library of derivatives containing wide variation in steric/electronic
properties. Steric parameters, such as Sterimol values, are predicted to produce linear free-energy relationships that correlate
to selectivity differences between 2° and 3° C–H bonds, or between sterically differentiated 2° C–H bonds. Electronic
parameters, such as bond stretching frequencies, could correlate to selectivity differences between electronically
differentiated C–H bonds. The effects of each of these parameters on selectivity can then be combined using linear
regression algorithms to produce mathematical models that will allow identification of specific mediator characteristics
which control site selectivity. A key tenet of this approach is that all data points for selectivity will be included in the model,
because negative results (i.e. poor selectivity or selectivity for the wrong C–H bond) also give valuable information about
site-selectivity. A statistically robust model for selectivity will allow for the informed design of new mediators with
improved site selectivity. Improved mediators will be evaluated for their ability to facilitate site selective C–H oxidation in
a wider variety of substrates containing sterically and electronically differentiated C–H bonds.
 Additionally, a similar strategy will be concurrently pursued using 1,4-diazabicyclo[2.2.2]octane (DABCO) based
derivatives (Aim 2). DABCO derivatives are expected to be relatively easily synthesized, providing a general structure for
producing a library of steric and electronic variants. This wil...

## Key facts

- **NIH application ID:** 9921204
- **Project number:** 5F32GM129980-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jeremy Dale Griffin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921204

## Citation

> US National Institutes of Health, RePORTER application 9921204, Designed Mediators for Selective Electrochemical C H Oxidation (5F32GM129980-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9921204. Licensed CC0.

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