An Automated Electrochemical Flow Platform to Accelerate Library Synthesis and Reaction Optimization

Area of Science:

• Electrochemistry
• Flow Chemistry
• Medicinal Chemistry

Background:

• Automated batch and flow systems are established in thermal and photochemistry.
• Electrochemical platform development faces challenges in cell miniaturization and flow system design.

Purpose of the Study:

• To design and implement a new slug-based automated electrochemical flow platform.
• To demonstrate the platform's utility in C-N cross-couplings for medicinal chemistry.
• To validate the platform's versatility through automated optimization.

Main Methods:

• Development of a slug-based automated electrochemical flow system.
• Application to electrochemical C-N cross-couplings with diverse amines.
• Utilizing Design of Experiments (DoE) for automated reaction optimization.

Main Results:

• Successfully demonstrated electrochemical C-N cross-couplings for 44 examples.
• Platform applicability for medicinal chemistry confirmed through continuous-flow transfer.
• Automated DoE optimization led to a 6-fold increase in reaction yield for a challenging target.

Conclusions:

• The developed platform addresses key limitations in automated electrochemistry.
• The system is versatile and applicable to medicinal chemistry synthesis.
• Automated optimization significantly enhances reaction efficiency and yield.