Direct electrochemical reductive amination between aldehydes and amines with a H/D-donor solvent

Area of Science:

• Organic Chemistry
• Electrochemistry
• Green Chemistry

Background:

• Reductive amination is a crucial reaction for synthesizing amines.
• Existing methods often require harsh conditions, metal catalysts, or external reductants.
• Developing sustainable and efficient synthetic protocols is essential in modern chemistry.

Purpose of the Study:

• To develop a novel, metal-free electrochemical protocol for reductive amination.
• To explore the dual role of DMSO as a solvent and hydrogen donor.
• To demonstrate the synthesis of deuterium-labeled amines and a biologically relevant molecule.

Main Methods:

• Electrochemical synthesis in undivided cells at room temperature.
• Metal-free and external-reductant-free electrolysis.
• Deuterium-labeling experiments using DMSO-d6.
• Sulfonylation for further functionalization.

Main Results:

• Successful reductive amination of aldehydes and amines yielding secondary amines in moderate to high yields.
• Demonstration of DMSO's function as both solvent and hydrogen donor.
• Synthesis of deuterium-labeled products with high deuterium incorporation.
• Preparation of a glucocorticoid receptor (GR) antagonist precursor.

Conclusions:

• The developed electrochemical protocol offers a sustainable and efficient route for reductive amination.
• This method avoids the need for metal catalysts and external reductants, aligning with green chemistry principles.
• The protocol is versatile, enabling the synthesis of diverse amine products and isotopically labeled compounds.