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

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $787,953

## Abstract

Project Summary: Discovery and Development of Organic Reactions
 Catalyzed by Transition-Metal Complexes Valuable for Medicinal Chemistry
 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 that are important for human health. Research on these reactions addresses several
of the major unmet needs in chemical synthesis: 1) the need for reactions that occur at C-H bonds with
high selectivities and high tolerance for auxiliary functional groups; 2) the need for reactions that occur with
catalyst-controlled site selectivity for one of many similar functional groups; 3) the need to functionalize
complex molecules directly to modulate the structures and properties of biologically active compounds; 4)
the need to assemble aliphatic sub-structures with control of the absolute and relative configurations of
stereogenic centers to create more complex three-dimensional architectures; and 5) the need for greater
mechanistic understanding of catalytic methods to help select or invent catalysts and reagents that achieve
these synthetic goals. The types of reactions proposed for study include some of the most widely used
catalytic reactions during the drug-discovery process. For example, these reactions include selective
functionalizations of C-H bonds to form main group compounds that have become common synthetic
intermediates. The proposed research further includes C-H bond functionalizations that form organic
azides and halides that can serve as intermediates or biogically important final products. The proposed
research also encompasses reactions occuring in aliphatic structures by addition and substitution
reactions, including the addition of N-H bonds across unactivated alkenes with unprecedented efficiency,
coupling processes forming carbon-heteroatom bonds with organic electrophiles that have rarely coupled
with heteroatom nucleophiles, and coupling processes forming carbon-heteroatom and carbon-carbon
bonds with unique control over the combination of regioselectivity, enantioselectivity, and
diastereoselectivity. New small-molecule catalysts also will be studied that reverse the typical site
selectivity observed for oxidation of alcohols, allowing modification of complex natural products, such as
polyols. Finally, the proposed research includes reactions catalyzed by a new class of hybrid system
generated by formally exchanging the metal of natural metalloenzymes with a platinum-group metal. These
artificial metalloenzymes can form products with site-selectivity and stereoselectivity that are difficult or
impossible 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 d...

## Key facts

- **NIH application ID:** 10316182
- **Project number:** 5R35GM130387-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** John F Hartwig
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $787,953
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316182

## Citation

> US National Institutes of Health, RePORTER application 10316182, Discovery and Development of Organic Reactions Catalyzed by Transition Metals Valuable for Medicinal Chemistry (5R35GM130387-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10316182. Licensed CC0.

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