# New catalytic methods for the rapid synthesis of N-unprotected chiral aziridines and amines

> **NIH NIH R35** · RICE UNIVERSITY · 2024 · $117,940

## Abstract

Project Summary
Amines and their derivatives are ubiquitous substances since they are present in the overwhelming majority of
drug molecules, agrochemicals, functional materials as well as many compounds that are produced by living
organisms (i.e., natural products). Notably, there are, on average, 2.8 nitrogen atoms in each of the 200 best-
selling small molecule drugs and, of these drugs, 80% contain at least one N-heterocyclic fragment. It is also
estimated that 45% of drug candidates contain a chiral amine moiety. Among these nitrogen-containing
compounds, aromatic and heteroaromatic amines (i.e., anilines) appear as core structures in more than one third
of drug candidates while aziridines, the three-membered and equally highly-strained nitrogen analogues of
epoxides, are important synthetic intermediates en route to structurally complex molecules due to their versatility
in myriad regio- and stereoselective transformations. Not surprisingly, organic chemists invest a considerable
amount of effort devising better strategies for synthesis of amines that serve as key chemical building blocks for
the preparation of biologically active compounds, especially in medicinal chemistry. These strategies can also
be used for late-stage functionalization of complex molecules that enables the exploration of new chemical space
for biological studies. Consequently, new and powerful synthetic strategies and methods for the rapid and direct
introduction of nitrogen into readily available and inexpensive precursors such as alkanes, alkenes, arenes,
heteroarenes as well as carbonyl compounds are expected to have a far-reaching impact upon how organic
synthesis, medicinal chemistry, biochemistry and chemical biology are practiced. In particular, the introduction
of unprotected nitrogen and other heteroatoms in a single step and under mild conditions will result in processes
that are more efficient and “greener” than currently used multi-step routes and ultimately will lead to the faster
development of new medicines.
During the course of the proposed project novel metal-catalyzed and organocatalytic amination processes will
be developed that will take advantage of both catalytically and stoichiometrically generated electrophilic
aminating agents. Thus, the direct synthesis of chiral as well as achiral primary and secondary anilines from
aromatic and heteroaromatic compounds, of alpha-aminated carbonyl compounds from ketones and carboxylic
acid derivatives, of fully-substituted amines from ketimines, ketoximes and ketiminoesters and of NH- as well as
N-alkylaziridines from isolated/unactivated olefins will be achieved. The proposed catalytic amination processes
will be thoroughly investigated to uncover and understand their mechanistic underpinnings. Emphasis will be
given to the development of reactions that can utilize abundant and inexpensive starting materials and convert
these to structurally complex/value added products under operationally simple and mild r...

## Key facts

- **NIH application ID:** 11047195
- **Project number:** 3R35GM136373-05S1
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Laszlo Kurti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $117,940
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047195

## Citation

> US National Institutes of Health, RePORTER application 11047195, New catalytic methods for the rapid synthesis of N-unprotected chiral aziridines and amines (3R35GM136373-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11047195. Licensed CC0.

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