# Switchable Organometallic Catalysts for Organic Reaction Development

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2024 · $114,467

## Abstract

Project Summary / Abstract
The discovery of new catalyzed methods to generate key bonds in organic molecules is vital to the sustainable
synthesis of biologically relevant molecules. The rapid diversification of simple chemical scaffolds using
automated parallel synthesis technologies allows for the generation of chemical libraries to screen for new
biological activity, and to assess structural-activity relationships, which facilitates the design of novel medicinal
targets with improved activity. New catalytic methods for parallel synthesis benefit from catalysts that can
selectively functionalize one site on the chemical scaffold, without changing other reactive functionalities on the
molecule. Developing a single catalyst that can select one reactive functionality, and then be switched to select
and react at a different site on the molecule, will allow sequential control of iterative reactions, thereby building
advanced synthetic targets in one pot using a strategy amenable to automated technologies. The proposed work
is centered on developing an organometallic catalyst with site-selective reactivity that can be switched by the
irradiation of different wavelengths of visible and ultraviolet light. The optimized organometallic catalysts will be
applied to iterative one-pot cross-coupling technologies, selectively activating either C(sp2)-X or C(sp3)-X bonds
for the formation of new carbon-carbon bonds depending on the external light stimulus. Investigation of the ability
of the switchable organometallic complex to undertake hydrogen-atom transfer from bound alcohols will also be
conducted, resulting in the oxidation of the alcohol in situ for subsequent reductive cross-electrophile coupling
strategies. This approach facilitates temporal control of the rates of the multiple catalytic cycles according to the
wavelength of the light irradiation and will be applied to the coupling of alcohols with a range of different
electrophilic species. These methodologies will enable the iterative formation of key biological motifs, such as
stereodefined polyol sequences, that can be used to study novel medicinal targets. The program will also train
a diverse group of graduate students, undergraduate students, and postdoctoral researchers in scientific
research encompassing organic, organometallic, and physical organic chemistry, and will provide these
colleagues with the professional development necessary to ensure success in their future careers.

## Key facts

- **NIH application ID:** 10938886
- **Project number:** 1R35GM155295-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Christopher Sandford
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $114,467
- **Award type:** 1
- **Project period:** 2024-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938886

## Citation

> US National Institutes of Health, RePORTER application 10938886, Switchable Organometallic Catalysts for Organic Reaction Development (1R35GM155295-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10938886. Licensed CC0.

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