Unveiling Organocatalysts Action – Investigating Immobilized Catalysts at Steady‐State Operation via Lab‐on‐a‐Chip Technology

Abstract

This paper reports a new method for studying stereoselective catalyzed reactions at a small scale. For this purpose, a micro‐sized chemical reactor and a chiral chromatographic column were integrated on a single microfluidic chip hyphenated to mass spectrometry. By running the integrated reactor in truly continuous‐flow operation with an automated injection strategy, catalytic processes and their stereoselectivity can be observed over an extended range of time with significantly small consumption of samples, solvents, and catalytic material.

An integrated resource-efficient microfluidic device for parallelised studies of immobilised chiral catalysts in continuous flow via miniaturized LC/MS-analysis

“…For the α-amination, almost identical signals could be observed as in the studies with the integrated chip system utilizing a single microreactor. 53 For the Mannich reaction with heptanaldehyde ( 1b ), three product peaks ( 5b ) were visible ( t R = 9.7 min, t R = 12.2 min, and t R = 14.0 min). However, four signals were expected, as presented before for the chip separation of the Mannich reaction with hydrocinnamaldehyde ( 1a ), which correspond to the syn - and anti -products and their respective ( S )- and ( R )-enantiomers ( 5b ).…”

“…These two reactions were chosen to enable almost direct comparability of the results with the single chip-reactor systems reported earlier. 52,53 Nevertheless, to evaluate if any cross-contamination between the two reactors is visible, heptanaldehyde ( 1b ) instead of hydrocinnamaldehyde ( 1a ) was used for the Mannich reaction for this first part to avoid using the same reactant in both reactors. Both reactors were operated simultaneously with alternating injections onto the integrated chiral HPLC column each 15 min.…”

“…In our previous publication, we have already presented the excellent long-term stability of the applied Ley–Arvidsson–Yamamoto catalyst in a study over three days with a continuous microreactor device. 53…”

“…In our previous publication, we have already presented the excellent long-term stability of the applied Ley-Arvidsson-Yamamoto catalyst in a study over three days with a continuous microreactor device. 53 We also implemented a fully automated injection sequence for the newly presented approach to enable similar long-term studies (automation described in detail in the ESI †). The previous experiment in MeCN was repeated with the same chip, simultaneously comparing the α-amination and Mannich reaction (with hydrocinnamaldehyde (1a) as a reactant for both reactions) over an extended runtime of 16.5 hours, performing alternating injections from the two reactors each 25 min (n total = 39).…”

“…51 Previously, we reported on two microfluidic systems, combining a packed microreactor either in a micro batch-like manner (stopped-flow), 52 or in continuous flow to an embedded chiral separation unit with subsequent MShyphenation by using only a minimized amount of catalytic material. 53 Combining multiple of these reactors in parallel as a single integrated unit could further increase analytical throughput for stereoselective catalytic process development. We extended our previously presented device with a second continuous reactor running in parallel to explore this potential.…”