# Supplement: Studies in the Synthesis of Complex Organic Molecules with Donor-Donor Carbenes

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $117,591

## Abstract

Project Summary/Abstract (from parent grant)
An urgent need exists for new methods to rapidly prepare complex molecules with the potential to become new
drugs. There is a widening gap in both the accessibility of complex core structures that are difficult to exploit and
in the availability of core structures that are not already the subject of numerous patents. This gap will be
addressed by identifying new synthetic methods that achieve the dual goals of enabling efficient access to useful
cores and exploring previously inaccessible "chemical space." The long-term goal of our research program is to
understand the reactivity of unstabilized metal carbenes. The objective of this application is to explore the ability
of rhodium donor-donor carbenes to engage in a wide variety of useful new applications. The central hypothesis
is that appending two "donor" groups to a carbene opens up new avenues of reactivity for organic chemistry.
This hypothesis is supported by preliminary results regarding a) the unique ability of donor/donor carbenes to
engage in highly enantioselective C–H insertion reactions and b) a new mild and catalytic process for the
formation of reactive dienes for cycloaddition reactions! Small molecules comprise the vast majority of treatments
for both acute and chronic diseases in both the developed and developing world. Research in this application
will lay the groundwork to save lives and enable the next generation of pharmaceutical discovery by focusing on
three areas of research. First, we will explore new C–H insertion reactions the enable the synthesis of complex
carba- and heterocyclic structures, culminating in an efficient synthesis of polycyclic alkaloid natural products
that will be studies for the ability to induce neuroplasticity for the treatment of PTSD, depression and other
neurological disorders. Second, we will explore new reactions of rhodium donor-donor carbenes that branch out
form C–H insertion into new reactions that access new chemotypes. Finally, we will, for the first time, build a
QSSR model that will enable the design, synthesis and exploration of new catalysts that are custom-designed
to enhance the reactivity of donor-donor carbenes. The proposed approach is innovative because it is based on
a new methodological platform that enables previously inaccessible chemical reactivity. This research is
significant because it will change the way synthetic chemists approach targets while at the same time opening
up new vistas for discovery of useful molecules for medicine and other fields. Ultimately, the discoveries
emerging from our research will represent a vertical step in the assembly of molecular architectures that will
translate into new medicines to address our society's most pressing health challenges.

## Key facts

- **NIH application ID:** 11029481
- **Project number:** 3R35GM149209-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jared Thomas Shaw
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $117,591
- **Award type:** 3
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11029481

## Citation

> US National Institutes of Health, RePORTER application 11029481, Supplement: Studies in the Synthesis of Complex Organic Molecules with Donor-Donor Carbenes (3R35GM149209-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11029481. Licensed CC0.

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