Enantioselective Sensing in the Fluorous Phase for Catalyst Screening: Application of a Racemic Fluorescent Probe.

Abstract

A perfluoroalkyl ketone-based molecular probe was found to show highly enantioselective fluorescent enhancement in the fluorous phase when treated with an amino alcohol generated from the asymmetric reaction of a meso-epoxide with an alkyl amine. The two enantiomeric probes (R)- and (S)-2 were used to screen catalysts for this asymmetric reaction. The use of the probe in the fluorous phase allowed the fluorescent sensing of the products to be conducted away from the other reaction components with minimized interference. It was further found that when (R)- or (S)-2 was used to determine the enantiomeric composition of the amino alcohol product, there was a large nonlinear effect. That is, only when one enantiomer of the substrate was in excess was there a large fluorescence enhancement for the chirality-matched probe-substrate interaction. This allowed the racemic probe rac-2 to be used to evaluate the asymmetric induction in the catalyst screening. The catalyst screening using the fluorescent probes led to the discovery of a more enantioselective and efficient method for the desymmetrization of 1,2-epoxycyclohexane with iPrNH2 to form the corresponding chiral amino alcohol. This work presents a novel method to conduct catalyst screening for asymmetric synthesis and has potential to become a high-throughput process.