eCyclopropanation - a safe and scalable electrochemical route to cyclopropanes

Area of Science:

• Organic Synthesis
• Electrochemistry
• Catalysis

Background:

• Diazo compounds are versatile synthetic intermediates but are unstable and hazardous, limiting their large-scale application.
• Current methods require isolation or accumulation of diazo species, posing safety risks.

Purpose of the Study:

• To develop a safe, scalable, and operationally simple electrochemical strategy for in situ diazo compound generation.
• To couple this generation directly with Rh(ii)-catalyzed cyclopropanation reactions.

Main Methods:

• Electrochemical oxidation of tert-butylhydrazones for in situ diazo generation.
• Continuous generation and consumption of diazo intermediates.
• Rh(ii)-catalyzed cyclopropanation using the transiently generated diazo species.

Main Results:

• Successfully generated diazo compounds in situ without accumulation, significantly improving safety.
• Achieved high yields of cyclopropanes across a diverse range of substrates.
• Demonstrated scalability and translation to continuous flow processes.

Conclusions:

• The developed electrochemical method provides a safe and sustainable alternative for diazo chemistry.
• This transient operation mode removes a key barrier to the industrial application of diazo compounds.
• Presents a blueprint for safer, industrially relevant carbene-transfer processes.