# Catalytic chiral aziridination with earth abundant metals

> **NIH NIH R15** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2020 · $381,806

## Abstract

Catalytic chiral aziridination with earth abundant metals
 The aziridine functional group, which is a three-membered heterocycle with one nitrogen and
two carbons, is critically important in biology and, therefore, also in synthetic medicinal chemistry.
Aziridines are found in natural products, such as mitomycins, azinomycins, ficellomycins, and
thiotepa, that have antitumor and antibiotic properties. Additionally, the strained aziridine, which
stores ~27 kcal/mol of energy, can be ring opened with a wide variety of nucleophiles, including
N-, O-, and C-based examples, in a manner analogous to epoxides. Furthermore, aziridines can
undergo an extensive variety of ring expansion reactions including, recently, the first [3+2]
annulation.
 Yet one can only take advantage of these ring opening and ring expansion reactions if there
is an easy way to prepare aziridines in a manner similar to epoxides and cyclopropanes. Despite
lying between carbon and oxygen on the periodic table, the nitrogenous version of this ring
forming reaction, aziridination, lags far behind by any number of metrics, specifically in their ability
to be synthesized catalytically. In fact, the most common methods for forming aziridines are
stoichiometric ring closing reactions, such as the Wenker synthesis (developed almost a century
ago) which is the closing of a linear 1,2-amino-alcohol under acidic conditions. To date, there
are no commercially available, broadly effective catalysts for aziridination between an
alkene and nitrene moiety. Our objective is to develop a general catalytic cycle with earth
abundant metals for a C2 + N1 aziridination reaction featuring a wide variety of alkenes (C2) and
organic azides (N1). Crucially, earth abundant metals, such as iron, will reduce costs during both
synthesis and the purification steps to remove metals during drug development since earth
abundant metals are less toxic than heavy metals.
 In this proposal, we continue our research on catalytic aziridination to include new directions
relevant to the medicinal chemistry community. Two specific limitations of our current catalyst
system that render it inexpedient for medicinal chemistry will be addressed. These limitations
include the necessity for excess alkene relative to organic azide and the lack of an
enantioselective version of our catalytic system. Since most leading drug candidates with
aziridine intermediates feature chiral aziridines, this breakthrough will revolutionize C2 +
N1 aziridination for medicinal chemistry.

## Key facts

- **NIH application ID:** 10114556
- **Project number:** 2R15GM117494-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** David M. Jenkins
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,806
- **Award type:** 2
- **Project period:** 2016-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114556

## Citation

> US National Institutes of Health, RePORTER application 10114556, Catalytic chiral aziridination with earth abundant metals (2R15GM117494-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10114556. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*