# Metal-Catalyzed Reactions for Organic Synthesis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $377,431

## Abstract

PROJECT SUMMARY
 Overall, this program will develop a variety of new metal-catalyzed synthetic methods for the construction
and late-stage diversification of biologically relevant molecules. The proposed work encompasses many different
types of chemical reactions but is unified by two central themes. First, it focuses on developing transformations
that provide access to new chemical space and/or that streamline the synthesis of existing structures. Second,
the proposed efforts are guided by detailed mechanistic analysis and organometallic chemistry.
 A first project continues the Sanford group's long-standing efforts in developing new approaches to carbon–
hydrogen bond functionalization. The traditional approach in this area focuses on the discovery of highly selective
reactions, in which the catalyst, substrate, and reaction conditions are tailored to convert a single, specific C–H
bond into a new functional group. While successful, this approach is limited by a disproportionate focus on
relatively simple substrates that contain only one “reactive” C–H site. The proposed efforts will contribute to
shifting this paradigm by targeting reactions in which a single starting material is converted into multiple C–H
functionalization products. This will provide access to new structures that are of high interest in medicinal
chemistry. Additionally, it will provide a wealth of mechanistic data about the factors responsible for reactivity
and selectivity that will be used to drive next-generation catalyst design and new reaction discovery.
 A second project will target the development of new metal-catalyzed cross coupling reactions. Notably, cross-
coupling is among the most widely used transformations in organic synthesis. The proposed efforts present a
unified approach to target three central challenges associated with modern cross-coupling methods: (1) the use
of abundant carboxylic acid-derived electrophiles as coupling partners; (2) elimination of the requirement for
added base; and (3) the invention of reactions that form new types of bonds, with a focus on introducing fluorine-
containing functional groups that are of high value in medicinal chemistry. All three goals will be accomplished
in an integrated fashion via a common mechanistic foundation.
 A third project leverages the Sanford group's expertise in organometallic chemistry, mechanistic analysis,
and catalytic reaction development to identify and tackle an emerging challenge in organic synthesis. SF5-
substituted (hetero)aromatic rings are gaining increasing prominence as entities for integration into drug
candidates. However, despite the growing significance of this functional group, synthetic methods for accessing
aryl–SF5 derivatives remain extremely limited. This proposal outlines fundamental studies of the synthesis and
reactivity of metal–SF5 complexes (species that are currently unprecedented). These studies will then be used
to drive the development of catalytic aryl–SF5 coupling ...

## Key facts

- **NIH application ID:** 10120706
- **Project number:** 5R35GM136332-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MELANIE S. SANFORD
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,431
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120706

## Citation

> US National Institutes of Health, RePORTER application 10120706, Metal-Catalyzed Reactions for Organic Synthesis (5R35GM136332-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120706. Licensed CC0.

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