# Nickel-Catalyzed Alkyne Hydroamination for Efficient Amine Synthesis

> **NIH NIH R15** · NORTH DAKOTA STATE UNIVERSITY · 2021 · $414,750

## Abstract

PROJECT SUMMARY
 Amines are ubiquitous subunits of biologically active compounds. Transition metal-catalyzed
hydroamination enables atom-efficient synthesis of amines using readily available chemical
feedstocks. Many classes of metal catalysts and ligands have been developed to facilitate
hydroamination of alkynes, generating enamine and imine products that are valuable building
blocks for nitrogen-containing molecules. In spite of these advances, catalytic alkyne
hydroamination faces several major challenges including the high costs of catalysts that are largely
based on precious metals, the common requirement of high reaction temperatures, as well as the
long-standing hurdle of regiochemistry control. Overcoming these challenges would widen practical
applications of catalytic alkyne hydroamination in biomedical research and drug synthesis.
 The long-term goal of our proposed research is to develop earth-abundant transition metal-
based catalysts to promote selective and efficient synthesis of amines and other nitrogen-
containing compounds. The overall objective of this research is to advance the reaction scope and
catalyst efficiency for nickel-catalyzed alkyne hydroamination processes. Our research strategy
emphasizes on in-depth reaction mechanism understanding by experimental and computational
methods, which will guide our efforts on hydroamination catalyst optimization and development of
mechanistically relevant aminative tandem transformations. Our proposed studies are based on
the central hypothesis that N-heterocyclic carbene (NHC)-ligated nickel complexes possess unique
reactivity of N-H bond activation and C-N bond formation at low energy barriers, which unlocks a
broad scope of alkyne hydroamination and relevant catalytic processes under mild and neutral
conditions. Feasibility of this research is demonstrated by our published and unpublished results
on Ni/NHC-catalyzed alkyne hydroamination with various N-H nucleophiles including biomedically
important heteroaryl-amines, as well as reactivity evaluation of structurally characterized novel Ni-
NHC complexes with amide-type ligands.
 Guided by strong preliminary data, we propose to pursue the following two Specific Aims:
(1) To advance the scope and functional group compatibility of Ni/NHC-catalyzed alkyne
hydroamination. (2) To define the mechanism of Ni/NHC-catalyzed alkyne hydroamination.
 Our proposed research is innovative because it aims to exploit unique bond-transformation
reactivity of Ni/NHC complexes for alkyne hydroamination. Results from these proposed studies
are significant because they will provide new and efficient catalytic methods for transformations of
simple building blocks to synthesize nitrogen-containing small molecules of biomedical relevance.

## Key facts

- **NIH application ID:** 10292302
- **Project number:** 1R15GM143712-01
- **Recipient organization:** NORTH DAKOTA STATE UNIVERSITY
- **Principal Investigator:** Pinjing Zhao
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $414,750
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292302

## Citation

> US National Institutes of Health, RePORTER application 10292302, Nickel-Catalyzed Alkyne Hydroamination for Efficient Amine Synthesis (1R15GM143712-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10292302. Licensed CC0.

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