Asymmetric reaction discovery has been fueled by the advent of high-throughput screening (HTS). A HTS approach enables for thousands of reaction conditions to be screened in parallel; however, a significant bottleneck is encountered upon reaction analysis due the sheer volume of reactions that were performed. The most common method for determining the success of an asymmetric transformation is chiral chromatography but the serial nature of analysis is not readily amenable to HTS protocols. To address this bottleneck, optical methods such as UV-Vis, fluorescence and circular dichroism (CD) spectroscopy have been employed to determine the yield and enantioselectivity of a given asymmetric transformation. While this approach has had much success, this strategy has not been applied to a transformation that is both enantio- and diastereoselective. Such a strategy necessitates the ability to differentiate enantiomers and diastereomers as well as quantify total substrate concentration. Herein, we report the utilization of dynamic covalent chemistries for the differentiation of the four stereoisomers of 2-amino-cyclohexanol. Incorporation of the mono-ols into a tripodal tris(pyridyl) ligand and complexation to a zinc(II) center followed by chiroptical analysis allowed for the stereochemistry at the 1-position to be probed. Imine formation between the chiral aminoalcohol and 3-hydroxy-pyridine-2-carboxaldehyde and subsequent complexation to an iron(II) center relayed the stereochemical information at the 2-position using exciton-coupled circular dichroism while UV-Vis analysis of the same octahedral iron complex allowed for the differentiation of the syn- and anti- 1,2-aminoalcohols. The optical triage was supplemented with a yield assay to quantify the total concentration of the 1,2-aminoalcohols via hydrazone formation and fluorescence spectroscopy.

Rapid optical determination of ee, de, and total concentration: A demonstration using 2-aminocyclohexanol

2019 Spring National Meeting

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