# Discovery and Development of Organic Reactions Catalyzed by Transition Metals Valuable for Medicinal Chemistry

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $48,469

## Abstract

Catalysts and Catalytic Reactions for the Synthesis of Medicinally Relevant Organic Compounds
The proposed research focuses on the discovery, development, and mechanistic evaluation of a series of
chemical reactions catalyzed by transition-metal complexes that provide new approaches to the synthesis
of organic molecules important for human health. Research on these reactions addresses several of the
major unmet needs in chemical synthesis. These unmet needs include reactions that occur at C-H bonds
with high selectivities and high tolerance for auxiliary functional groups; the creation of catalysts that induce
chemical reactions at one of many potential reaction sites in complex structures; catalytic transformations
of complex molecules to modulate the structures and properties of biologically active compounds;
assembly of aliphatic sub-structures with control of the absolute and relative configurations of stereogenic
centers to create more complex three-dimensional architectures; and greater mechanistic understanding
of catalytic methods to help select or invent catalysts and reagents that achieve these synthetic goals. This
program focuses on the development and mechanistic understanding of catalytic reactions that are some
of the most widely used reactions during drug-discovery and production, as well as reactions poised to
become the next set of such reactions and classes of catalysts that can lead to new capabilities. These
reactions include selective functionalization of C-H bonds with main group reagents to form valuable
synthetic intermediates, reactions to form alkyl C-N bonds by addition of N-H bonds across alkenes with
unprecedented efficiency, coupling processes to form carbon-heteroatom bonds with organic electrophiles
catalyzed by copper and nickel systems, and reactions catalyzed by an unusual class of hybrid structure
generated by formally exchanging the metal of natural metalloenzymes with an organometallic unit to
create artificial metalloenzymes that form products with site-selectivity and stereoselectivity that would be
difficult to achieve with natural enzymes or small-molecule catalysts. In all cases, the proposed research
includes detailed mechanistic analysis by kinetic stuides and independent synthesis of catalytic
intermediates, as well as the use of these mechanistic data to select or design next-generation systems. A
particular focus of these mechanistic studies will be placed on revealing the properties of recently
discovered catalysts for the functionalization of primary alkyl C-H bonds and recently discovered copper
and nickel intermediates in catalytic cross coupling reactions to form carbon-heteroatom bonds.

## Key facts

- **NIH application ID:** 10830116
- **Project number:** 3R35GM130387-06S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** John F Hartwig
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $48,469
- **Award type:** 3
- **Project period:** 2019-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830116

## Citation

> US National Institutes of Health, RePORTER application 10830116, Discovery and Development of Organic Reactions Catalyzed by Transition Metals Valuable for Medicinal Chemistry (3R35GM130387-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10830116. Licensed CC0.

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