# Heterogeneous Directed Hydrogenation of Arenes and Olefins with Chemo- and Stereoselectivity

> **NIH NIH R35** · PURDUE UNIVERSITY · 2024 · $373,453

## Abstract

Project Summary/Abstract
Heterogeneous noble metal catalysts are commonly used in organic synthesis for the
hydrogenation of unsaturated organic functionality because of their fast reactivity and ease of
purification. However, heterogeneous catalysts tend to be poorly selective in the presence of other
reducible functionality and incapable of achieving stereoinduction due to the two-dimensional
nature of the catalyst surface. Taking inspiration from the homogeneous literature on substrate-
directed reactivity, the Li group recently demonstrated the first example of a heterogeneous
hydroxyl-directed hydrogenation. Using a bimetallic alloy catalyst containing a noble metal and a
base metal, we were able to catalyze highly diastereoselective hydrogenations of cyclic olefins
by simultaneously adsorbing the hydroxyl directing group onto the base metal atom and the olefin
onto the noble metal site.
The overarching goal of this proposed research is to demonstrate that directed reactivity using
bimetallic alloys is a general strategy to achieve chemo- and stereoselective hydrogenation of
drug-like compounds. These selective hydrogenation reactions will be utilized to increase the sp3
content, three-dimensionality, and structural diversity of pharmaceutical candidates. We will
develop new bimetallic nanoparticle compositions in order to extend the directed hydrogenation
concept to systems that are not accessible using molecular catalysts, including arenes and
heteroarenes, amine-directed reactions, and substrates where the directing group and reactive
moiety are located remote from one another. We will also explore directing effects in dictating
chemo- and regioselectivity in substrates where multiple reducible functional groups are
simultaneously present. In parallel with the development of synthetic methods, we will conduct
detailed nanomaterials characterization, in-situ surface spectroscopy, and kinetic studies in order
to elucidate the surface ensemble required for high directivity. Together, this research program
will provide new heterogeneous catalysts and methods for selective, late-stage transformations
in biologically-active compounds.

## Key facts

- **NIH application ID:** 10890118
- **Project number:** 5R35GM151120-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Christina W Li
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,453
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890118

## Citation

> US National Institutes of Health, RePORTER application 10890118, Heterogeneous Directed Hydrogenation of Arenes and Olefins with Chemo- and Stereoselectivity (5R35GM151120-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10890118. Licensed CC0.

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