An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

Abstract

An integrated lab‐on‐a‐chip enables the rapid analysis of heterogenized enantioselective organocatalysis at the microscale. A packed‐bed microreactor was seamlessly integrated with a downstream chiral high pressure liquid chromatography (HPLC) functionality to study enantioselective transformations on a single microfluidic glass chip. Hyphenation to mass spectrometry allows for the rapid investigation of the selectivity and the substrate scope of microgram amounts of catalyst beads. Optimization of reaction conditions is possible with minimal reagent consumption and instant analytical feedback.

In situ monitoring of photocatalyzed isomerization reactions on a microchip flow reactor by IR-MALDI ion mobility spectrometry

“…The latter can be realized by applying spectroscopic techniques, such as fluorescence or Raman microscopy, or by coupling microfluidic chips to mass spectrometry. For isomer discrimination, we previously reported the integration of microflow reactions and chip HPLC [7][8][9] that allowed for the analysis of enantioselective transformations.…”

“…Microchip used in this study. b Layout of chip setup in front of IM spectrometer inlet with a side view of the microfluidic chip (1), the IM spectrometer inlet (2), the LED positioned in front of the chip reactor region (3), the LED cooler (4), the counter electrode (5), the laser beam (6), a PTFE insulation plate (7), the capillary system and microchip mount including clamps(8), and a fine positioning stage(9). c Inhouse-built IR-MALDI IM spectrometer with heated inlet in top view, inlet (2) at the bottom-left is equivalent to (2) of panel b, the pump inlet (10), the pulsed ion inlet (11), the drift tube(12), and the faraday plate (13) as the detection element…”

A Visible‐Light‐Powered Polymerization Method for the Immobilization of Enantioselective Organocatalysts into Microreactors

“…Initially, the flow‐through behavior of the fabricated device was evaluated using the asymmetric α‐amination of aliphatic aldehyde 1 with dibenzyl azodicarboxylate (DBAD) 2 as the benchmark (Scheme ). This model reaction was performed under the conditions previously employed with the silica‐supported counterpart for a direct comparison . This on‐line HPLC/MS analysis revealed the formation of adduct 3 with a much higher enantiomeric excess (50 % vs. 6 % ee ).…”

“…This model reaction was performed under the conditions previously employed with the silica-supported counterpart for ad irect comparison. [55] Thiso n-line HPLC/MS analysisr evealed the formation of adduct 3 with a much higher enantiomeric excess (50 %v s. 6% ee). Furthermore, the low pressure drop of just 1bar at the applied flow rate of 0.2 mLmin À1 allows operating the setup with economic low pressure pumps.…”

“…The approachd escribed here is based on previousw ork which focused on the fabrication of polystyrenem onolithic microreactors functionalized with the Ley-Arvidsson-Yamamoto (S)-5-(pyrrolidin-2-yl)-1H-tetrazole organocatalyst [54] as well as on the TMS-protected Hayashi-Jørgensen (HJ) catalysti mmobilized on silica and its applicationi nc hip devices with multiple functionalities. [55] For the latter approach, one challenge was the rather elaborate multi-step process for the creation of packed bed reactors inside microfluidic chips including the synthesis of the catalyst particlesa nd the slurry packing process. Herein, aone-step photo-initiated immobilization strategy for the TMS-protected HJ catalysto nm onolithic poly(styreneco-divinylbenzene) is presented and its activity tested in enantioselective CÀNÀ and CÀC-bond forming flow reactions.…”