# Fluorescence Microscopy for the Development of Organometallic Reagents and Catalysts from Metal Powders

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $319,284

## Abstract

Project Summary
 The long-term objective of this research program is to develop imaging approaches to enable the next
generation of mechanistic studies in synthetic chemistry. The overall objective for this application is to
determine the mechanistic roles of additives and solvents in enabling the direct insertion reactions of
organohalides to commercial metal powders, through the development of sensitive fluorescence microscopy
techniques. The direct insertion of organohalides to commercial metal powders would be the most convenient,
atom-economical, and potentially cost effective synthesis for a wide range of organometallic reagents and
catalysts across the periodic table, but it currently works for only a few metals (e.g., magnesium to make
Grignard reagents). The generalization of this direct insertion process has long been hampered by the
resistance of most commercial metal powders toward oxidative addition. Specific solvents or additives such as
salts cause a handful of initially unreactive metals to become active (e.g., indium or zinc with lithium chloride in
the “Knochel protocol”). The mechanistic roles of these additives and solvents, however, are largely unknown.
This lack of knowledge arises from the difficulty in detecting small quantities of intermediates in the field of
mechanistic chemistry, and this lack is limiting the development of direct insertion reactions for stoichiometric
and catalytic systems. Both of these gaps are overcome by the experiments in this proposal with fluorescence
microscopy. The central hypothesis is that new intermediates that provide guiding insight into the synthesis of
organometallic reagents and into the development of catalytic reactions can be discovered through sensitive
fluorescence microscopy with novel imaging agents. This approach is innovative because it develops tools for
mechanistic investigations at the single-molecule and -particle level, whereas traditional mechanistic tools are
best suited to measuring only the major components in mixtures. The central hypothesis will be tested by
pursuing three specific aims: 1) Determine the mechanistic origin of the salt and solvent effects on the direct
insertion reactions of organohalides to commercial metal powders of aluminum, indium, and zinc, and use this
knowledge to expand synthetic access to organoindium reagents from organochlorides; 2) Determine the role
of salts in the formation of organozinc reagents from Rieke zinc; and 3) Identify additives that enable direct
insertion to commercial copper and palladium powders, wherein such additive effects are essentially unknown.
The impact of the proposed experiments is two-fold: 1) They will provide guiding mechanistic information for
the development of synthetically useful reactions directly from commercial metal powders, and 2) They will
develop new mechanistic tools for synthetic chemists with sensitivity as high as single-molecule detection.
These studies will be among the first of any such sin...

## Key facts

- **NIH application ID:** 10380672
- **Project number:** 5R01GM131147-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Suzanne A. Blum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $319,284
- **Award type:** 5
- **Project period:** 2019-06-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380672

## Citation

> US National Institutes of Health, RePORTER application 10380672, Fluorescence Microscopy for the Development of Organometallic Reagents and Catalysts from Metal Powders (5R01GM131147-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380672. Licensed CC0.

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