Rapid catalyst screening by a continuous-flow microreactor interfaced with ultra-high-pressure liquid chromatography.
A high-throughput screening system for homogeneous catalyst discovery has been developed by integrating a continuous-flow capillary-based microreactor with ultra-high-pressure liquid chromatography (UHPLC) for fast online analysis. Reactions are conducted in distinct and stable zones in a flow stream that allows for time and temperature regulation. UHPLC detection at high temperature allows high throughput online determination of substrate, product, and byproduct concentrations. We evaluated the efficacies of a series of soluble acid catalysts for an intramolecular Friedel-Crafts addition into an acyliminium ion intermediate within 1 day and with minimal material investment. The effects of catalyst loading, reaction time, and reaction temperature were also screened. This system exhibited high reproducibility for high-throughput catalyst screening and allowed several acid catalysts for the reaction to be identified. Major side products from the reactions were determined through off-line mass spectrometric detection. Er(OTf)(3), the catalyst that showed optimal efficiency in the screening, was shown to be effective at promoting the cyclization reaction on a preparative scale.
Fang
Hui
H
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Xiao
Qing
Q
Wu
Fanghui
F
Floreancig
Paul E
PE
Weber
Stephen G
SG
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004871:Erbium / Q000737:chemistry*; D017022:Flow Injection Analysis / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D013696:Temperature
D004871:Erbium