Capillary-based microreactor for high throughput catalyst screening in Lewis acid and strong Brønsted acid catalyzed reactions

摘要

The microreactor technique has received considerable research attention due to its promising applications in organic chemistry. Compared to traditional organic synthesis, the employment of microreactor has several advantages. First, the small diameter of the microchannel can reduce the reagent mixing time to milliseconds, allowing fast heat transfer and thermal equilibrium. Second, higher yield and better selectivity are often observed for reactions carried out in a microreactor. Most importantly, reaction optimization and catalyst library generation can be rapidly achieved by the microreactor with reagents on a small scale.udIn the past few years, our group has been developing a capillary-based microreactor system that is capable of high throughput catalyst screening. This system consists of HPLC apparatus, syringe pumps and capillary tubings, which are all commonly used in the chemistry laboratory. Compared with the traditional chip-based microreactor, our system is easy to operate, and simple to modify. Additionally, it couples with gas chromatography (GC) or high-performance liquid chromatography (HPLC) for online analysis, providing near-real-time reaction monitoring. udOne of the applications we explored with our microreactor system was the homogeneous catalysis reaction. The first reaction tested was lanthanide-triflate catalyzed allylation of benzaldehyde with tetraallyltin. With GC online analysis, the reaction was successfully carried out in our microreactor system. The optimized reaction condition, 10% catalyst load/60 min reaction time in room temperature, was much milder compared with any published bench top conditions. The screening of 8 different catalysts for the reaction was accomplished within 2 hours, which led to a significantly shortened optimization time. udThe online enantiomeric separation analysis method was developed for a strong chiral Brønsted acid catalyzed asymmetric cyanide addition. Six chiral columns and various separation conditions were involved in the method development. Due to the incompatible issue between the reaction solvent and column bonded phases, a GC method was optimized and chose as our interfaced online analysis method. ud