Rapid catalyst screening by a continuous-flow microreactor interfaced with ultra-high-pressure liquid chromatography

Area of Science:

• Organic Chemistry
• Catalysis
• Chemical Engineering

Background:

• Homogeneous catalyst discovery is crucial for efficient chemical synthesis.
• Traditional screening methods can be time-consuming and resource-intensive.

Purpose of the Study:

• To develop an integrated high-throughput screening system for homogeneous catalyst discovery.
• To evaluate soluble acid catalysts for an intramolecular Friedel-Crafts addition reaction.

Main Methods:

• Integration of a continuous-flow capillary-based microreactor with ultra-high-pressure liquid chromatography (UHPLC).
• Online analysis of substrate, product, and byproduct concentrations at high temperatures.
• Screening of catalyst loading, reaction time, and temperature for an intramolecular Friedel-Crafts addition.

Main Results:

• The system demonstrated high reproducibility for high-throughput catalyst screening.
• Several effective acid catalysts were identified for the cyclization reaction.
• Erbium triflate (Er(OTf)(3)) was identified as the optimal catalyst and validated on a preparative scale.

Conclusions:

• The developed system enables rapid and efficient homogeneous catalyst discovery.
• The integrated microreactor-UHPLC system is suitable for optimizing reaction conditions and identifying catalysts.
• The identified catalysts, particularly Er(OTf)(3), show promise for scalable organic synthesis.