In Situ Evaluation of Kinetic Resolution Catalysts for Nitroaldol by Rationally Designed Fluorescence Probe

Development of effective chemical catalysts is a key concern in organic chemistry. Therefore, convenient screening systems for chemical catalysts are required, and although some fluorescence-based HTS systems have been developed, little attempt has been made to apply them to asymmetric catalysts. Therefore, we tried to develop a chiral fluorescence probe which can evaluate the reactivity and enantioselectivity of asymmetric catalysts. We focused on kinetic resolution catalysts as a target of our novel fluorescence probe, employing beta-elimination following acylation of nitroaldol. Once the hydroxyl group of nitroaldol is acylated, beta-elimination occurs immediately, affording nitro olefin. Therefore, we designed and synthesized a fluorescence probe with an asymmetric nitroaldol moiety. Its fluorescence intensity decreases dramatically upon beta-elimination, so the fluorescence decrease is an indicator of the read:ion yield. Thus, the enantioselectivity of kinetic resolution catalysts can be assessed simply by measuring the fluorescence intensities of the reaction mixtures of the two enantiomers; it is not necessary to purify the product. This fluorescence probe revealed that benzotetramisole is a superior catalyst for kinetic resolution of nitroaldol. Furthermore, we established an HTS system for asymmetric catalysts, using a fluorescence probe and benzotetramisole. To our knowledge, this is the first fluorescence-based HTS system for asymmetric catalysts.