An Initiator-Free Electrochemical Approach to Radical Thiol-Ene Coupling in a Microfluidic Reactor

Area of Science:

• Organic Chemistry
• Green Chemistry
• Electrochemistry

Background:

• Radical thiol-ene reactions are vital for synthesizing unsymmetrical sulfides, used in pharmaceuticals and materials.
• Conventional methods rely on metal or organic photosensitizers, posing environmental and product isolation challenges.
• There is a need for sustainable and efficient alternatives to traditional radical thiol-ene couplings.

Purpose of the Study:

• To develop an initiator-free thiol-ene coupling method using electrochemical oxidation.
• To explore the feasibility of using microfluidic electrochemical reactors for this transformation.
• To investigate the influence of substrate properties on reaction efficiency.

Main Methods:

• Electrochemical oxidation of thiols to generate thiyl radicals.
• Utilizing a microfluidic electrochemical reactor for controlled radical generation and reaction.
• Performing substrate scope studies with various alkenes and thiols.

Main Results:

• Successful demonstration of initiator-free thiol-ene coupling via electrochemical oxidation.
• Thioethers were synthesized in reasonable yields using the microfluidic electrochemical reactor.
• Reaction efficiency was found to depend on thiol acidity (pKa), alkene electronics, and steric factors.

Conclusions:

• Electrochemical oxidation provides a sustainable and initiator-free pathway for thiol-ene coupling.
• The microfluidic electrochemical approach offers a greener alternative to conventional methods.
• Further optimization is needed to enhance yields and expand substrate applicability for broader synthetic use.