# Catalytic Oxidations for Pharmaceutical Synthesis

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $363,331

## Abstract

Project Summary
Oxidation reactions are among the most important reactions in organic chemistry and play a crucial role in the
synthesis of pharmaceuticals, natural products, and other bioactive compounds. Advances in catalytic oxidation
reactions have potential for major impact in the discovery and production of pharmaceuticals. The majority of
existing catalytic oxidation methods face challenges in their efficiency and selectivity, including chemo-, regio-
and stereoselectivity, limiting their use in small- and large-scale applications. The proposed research will develop
new oxidation and oxidative coupling methods that form carbon-carbon and carbon-heteroatom bonds, including
C(sp3)–H functionalization reactions. Some of the resulting methods will streamline the discovery of new
bioactive molecules with diverse three-dimensional architectures, addressing key challenges in medicinal
chemistry and drug discovery, while others will provide the basis for streamlined process-scale synthesis of
pharmaceuticals. Three complementary project directions are outlined in this proposal. The first focuses on the
development of "oxidase"-type aerobic oxidation catalysts that feature a transition metal and a redox active
organic co-catalyst. New bioinspired catalyst systems will be explored that exhibit "second-order biomimicry",
whereby simple organic precursors undergo oxidative self-processing to create the essential co-catalysts. This
process resembles the post-translational modification of amino acid side chains to generate reactive cofactors
in Nature. The second project will pursue new electrochemical oxidation methods for the synthesis of organic
molecules that are difficult to access via classical synthetic methods. These efforts target the identification of
versatile mediators and electrocatalysts that permit the reactions to proceed at low electrode potentials, thereby
tolerating diverse functional groups and enabling broad scope and utility. Finally, we will develop "radical relay"
methods for benzylic C–H oxidation and oxidative coupling to afford new C(sp3) C–O, C–N, C–X, and C–C bonds.
These efforts will be applied to pharmaceutical building-block diversification, core-modification, and late-stage
functionalization. In each of these project areas, empirical reaction discovery efforts will be complemented by
mechanistic studies of the catalytic reactions. Close interactions and collaborations with pharmaceutical
companies in all phases of this project will play an important role in ensuring the broadest possible impact of our
efforts.

## Key facts

- **NIH application ID:** 9851605
- **Project number:** 1R35GM134929-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Shannon S Stahl
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,331
- **Award type:** 1
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851605

## Citation

> US National Institutes of Health, RePORTER application 9851605, Catalytic Oxidations for Pharmaceutical Synthesis (1R35GM134929-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851605. Licensed CC0.

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