# Catalysis of Tin-Free Radical Reactions Under H2

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $321,688

## Abstract

PROJECT SUMMARY/ABSTRACT
 Organotin reagents are routinely used to carry out radical reactions that create C-C bonds or effect the
reduction of certain functional groups. They are valuable tools for the small-scale, laboratory synthesis of
molecules for biochemical evaluation. Unfortunately, these tin reagents are unsuitable for use in
manufacturing, because they are difficult to remove and quite toxic. An alternative way of generating radical
intermediates is by the transfer of hydrogen atoms to unsaturated substrates from the hydride complexes of
first-row transition metals. Such hydrides are non-toxic and their use is sustainable: they can be regenerated
by hydrogen gas, so the generation of radicals by this method is catalytic. One H2 molecule produces two
hydrogen atoms — and two radicals — with almost no waste. This proposal seeks to determine which hydride
complexes can best do this chemistry and to identify new uses for radical reactions.
 First, the relative rates at which various alkenes and alkynes give radicals by this method will be
measured, and the uses of such radicals in cyclizations will be investigated. These radicals should be
particularly useful for cyclizations onto C=O, C=S, and C=N double bonds, and for the construction of three-
and four-membered all-carbon rings that are not readily available by other methods. Second, the formation of
radicals that do not cyclize can be followed by the transfer of another hydrogen atom in a separate step,
enabling the anti addition of H2 across a C=C bond. This reaction should permit the synthesis of natural
products that have been unavailable by traditional hydrogenation methods. Third, these new methods of
radical generation will be tested on natural product targets that have already been prepared via radicals
generated by established methods. The present syntheses have often been non-optimal; late-stage,
polyfunctional, substrates will be emphasized, in order to provide as effective a benchmark as possible for the
methods that have been developed. Successful catalytic reactions will then be applied to the synthesis of
pharmaceutically promising natural products that have not yet been prepared in the laboratory.
 Finally, hydride complexes — particularly anionic hydride complexes — may also be able to generate
radicals by electron transfer to appropriate halides R–X. It should be possible to regenerate these hydrides
under hydrogen with base, so these reactions can also be made catalytic. We will also test this new method of
radical generation on a natural product target that has been made with established methods.

## Key facts

- **NIH application ID:** 9902464
- **Project number:** 5R01GM124295-04
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** JACK R NORTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,688
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902464

## Citation

> US National Institutes of Health, RePORTER application 9902464, Catalysis of Tin-Free Radical Reactions Under H2 (5R01GM124295-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902464. Licensed CC0.

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