Supramolecular Methods for the Rapid Determination of Enantiomeric Excess in Reaction Screening
Prof. Eric V. Anslyn
Welch Regents Chair of Chemistry, Associate Chairman, University Distinguished Teaching Professor Department of Chemistry, University of Texas at Austin
Time & Place
Mon, 11 Sep 2017 11:00:00 NZST in Rutherford Room 532
All are welcome
The need for increasingly user-friendly and rapid assays for ee has arisen recently due the advent of parallel synthesis protocols for asymmetric reaction discovery and optimization. Many studies require hundreds to thousands of assays per day. A primary goal of our group is to design and implement high-throughput screening (HTS) assays for enantiomeric excess (ee) and reaction yield in catalytic asymmetric reaction screening. Our approach to the HTS of ee combines supramolecular chemistry, dynamic covalent bonding, and analytical instrumentation. We create very simple synthetic receptors or assemblies that are targeted to classes of chiral functional groups, and record absorbance or circular dichroism spectra for diastereomeric or enantiomeric complex formation. The analysis is performed in microtiter plates where the ee values of 96 crude reaction mixtures can be read within 10 minutes to 2 hrs depending upon the particular assay.
Further, linear free energy relationship (LFER) parameters are routinely used to parameterize physiochemical effects while investigating reaction mechanisms. In this presentation, we will describe an alternate application for LFERs: as training sets for model building in an analytical application. In this study, the sterics, quantified by Charton parameters (∆v), of nine secondary chiral alcohol analytes were correlated to the CD output from a chiral alcohol optical sensor. To test the model validity, the correlative linear model was applied to determine the enantiomeric excess of samples of two alcohols, without a priori knowledge of a calibration curve. The error in this method was comparable to previous experimental methods (<5%).
In addition, a new method for lowering the error of CD based methods for measuring high enantiomeric excess values will be described, which exploits the majority rules effect exhibited by certain helical polymers. A proof of principle experiment was conducted. Moreover, a new kind of supramolecular polymer, showing a racemate rules effect will be introduced.
Assays for diols, amines, carboxylic acids, ketones, and alcohols have been created. Several of these assays have been utilized in collaborations with synthetic methodology chemists throughout the nation. Examples of the assays, the physical organic underpinnings, along with practical applications will be presented.