Electrochemical DABCOylation enables challenging aromatic C-H amination

Area of Science:

• Organic Chemistry
• Electrochemistry
• Synthetic Methodology

Background:

• Selective amination of aromatic C-H bonds is crucial for synthesizing pharmaceuticals and agrochemicals.
• Existing methods struggle with electron-deficient (hetero)arenes and common pre-functionalization reactions.
• A general platform for direct, selective C-H amination across diverse arenes is needed.

Purpose of the Study:

• To develop a general and selective method for the direct C-H amination of a wide range of (hetero)arenes.
• To overcome limitations of current C-H functionalization techniques, especially for electron-deficient systems.
• To establish a sustainable electrochemical approach for synthesizing complex aryl amines.

Main Methods:

• Oxidative generation of electrophilic N-radical dications from bicyclic tertiary amines (DABCO).
• Electrochemical reaction enabling direct C-H amination across diverse arenes.
• Utilizing anodically generated N-radical cations for C-H amination.

Main Results:

• Achieved selective C-H amination across a comprehensive scope of (hetero)arenes, including electron-rich and electron-deficient systems.
• Demonstrated the first use of anodically generated N-radical cations for aromatic C-H amination.
• Provided access to complex drug-like aryl- and pyridinylpiperazines with high selectivity and functionality tolerance.

Conclusions:

• The developed electrochemical DABCOylation reaction offers a general solution for selective C-H amination of diverse (hetero)arenes.
• This method overcomes limitations in functionalizing challenging substrates and provides a sustainable synthetic route.
• The reaction enables efficient synthesis of valuable aryl amine derivatives with high chemo- and site-selectivity.