An Electrochemical Approach to Amine Synthesis from Nitrogen

NIH RePORTER · NIH · F32 · $73,828 · view on reporter.nih.gov ↗

Abstract

Project Summary/Abstract Nitrogen-containing functionalities constitute one of the largest classes within health-relevant small molecules. Therefore, the development of new methods to construct carbon–nitrogen bonds remains paramount among opportunities for innovation in chemical synthesis. The Haber–Bosch process is arguably the most important synthetic catalytic process, wherein atmospheric nitrogen (N2) is reduced to ammonia (NH3) by an iron catalyst under high temperature and pressure. In contrast, nature’s N2 fixation catalysts, nitrogenases, operate at ambient conditions using a bimetallic active site. As such, many well-defined coordination complexes have been developed to study key bond-forming steps in N2 reduction, with the goal of designing more efficient catalysts for the synthesis of ammonia and other value-added compounds. While there has been some success in catalytic N2 silylation to give tris(trialkylsilyl)amines, there are no examples of the analogous catalytic process for amine synthesis through carbon–nitrogen bond-formation from N2. Current strategies for the direct conversion of N2 amines require multistep synthetic sequences of metal–N2 complexes with organic electrophiles and subsequent product release under harsh conditions. To circumvent these limitations, the proposed research employs metallocene-based catalysts to promote proton-coupled electron-transfer pathways for radical functionalization of metal–N2 catalysts. Enabled by a renaissance in organic radical generation, easy access to a suite of abundant olefins, and by exploiting complementary reactivity modes of metal–N2 catalysts, a diverse range of primary, secondary, and aryl amine products can be synthesized. The research plan outlines specific approaches that will deliver fundamental insights into reactions of metal–N2 complexes with organic radicals and metal nitrides, commonly proposed intermediates in N2 reduction, with alkenes. These studies will provide the foundation for the realization of a catalytic synthesis of medicinally relevant functional groups from the most abundant source of nitrogen—N2.

Key facts

NIH application ID
10914036
Project number
5F32GM151784-02
Recipient
CALIFORNIA INSTITUTE OF TECHNOLOGY
Principal Investigator
John Michael Ovian
Activity code
F32
Funding institute
NIH
Fiscal year
2024
Award amount
$73,828
Award type
5
Project period
2023-08-09 → 2026-08-08