Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples

We have developed an optical method for accurate concentration, er, and dr analysis of amino alcohols based on a simple mix‐and‐measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. The conversion of the four aminoindanol stereoisomers with salicylaldehyde t...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2020-02, Vol.59 (6), p.2440-2448
Main Authors: De los Santos, Zeus A., MacAvaney, Sean, Russell, Katina, Wolf, Christian
Format: Article
Language:English
Subjects:
Absolute configuration
Absorption spectra
Alcohols
Algorithms
chirality sensing
circular dichroism
Direct reduction
Imines
Learning algorithms
Linear programming
Machine learning
Stereochemistry
stereoisomer analysis
Stereoisomers
Technology assessment
UV spectroscopy
Workflow
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Summary:We have developed an optical method for accurate concentration, er, and dr analysis of amino alcohols based on a simple mix‐and‐measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. The conversion of the four aminoindanol stereoisomers with salicylaldehyde to the corresponding Schiff base allows analysis of the dr based on a change in the UV maximum at 420 nm that is very different for the homo‐ and heterochiral diastereomers and of the concentration of the sample using a hypsochromic shift of another absorption band around 340 nm that is independent of the analyte stereochemistry. Subsequent in situ formation of CuII assemblies in the absence and presence of base enables quantification of the er values for each diastereomeric pair by CD analysis. Applying a linear programming method and a parameter sweep algorithm, we determined the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions with an averaged absolute percent error of 1.7 %. Stereo sensing: The combination of optical sensing and machine learning streamlines the analysis of small amounts of complex stereochemical mixtures of chiral compounds based on a simple mix‐and‐measure workflow that uses inexpensive chemicals while cumbersome protection chemistry and any type of sample work‐up are avoided.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201912904