# Development of Strategies for the Functionalization of Amines

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $283,010

## Abstract

Project Summary/Abstract
Nitrogen heterocycles are ubiquitous components of pharmaceutical drugs essential for
human health. A particularly attractive approach to nitrogen containing compounds is
the modification of cheap and readily available amines via C–H bond functionalization.
However, methods that efficiently accomplish this task typically require the use of
expensive transition metal catalysts and/or oxidants. This proposal is focused on the
design and development of efficient and practical methods for amine functionalization.
The main goal is the alpha-functionalization of amines through conceptually new and
underdeveloped methods of substrate activation. One tactic will achieve amine C–H
bond functionalization in redox-neutral fashion by combining a reductive amine N-
alkylation with an oxidative alpha-functionalization, utilizing azomethine ylides as
reactive intermediates. Water is generated as the only byproduct and the only required
promoters are cheap carboxylic acids. A second strategy facilitates the functionalization
of cyclic amines via a novel method involving intermolecular hydride transfer. This
approach does not require protecting groups and provides valuable secondary amine
products. Reactions are highly enantiospecific and enable late-stage functionalization of
drug candidates. A third goal is the direct transformation of simple cyclic amines to
alpha,beta-difunctionalized amines. This will be accomplished via a novel strategy that
involves azaallyl anions. In addition to targeting the rapid preparation of compounds
related to structures with known biological activities, efforts will center on the
development of particularly powerful reactions that rapidly produce new polycyclic
amines. A priority is the generation of new structural frameworks that are absent from
current drug discovery screening libraries.

## Key facts

- **NIH application ID:** 10104513
- **Project number:** 5R01GM101389-10
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Daniel Seidel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $283,010
- **Award type:** 5
- **Project period:** 2012-09-21 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104513

## Citation

> US National Institutes of Health, RePORTER application 10104513, Development of Strategies for the Functionalization of Amines (5R01GM101389-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104513. Licensed CC0.

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