A One-Pot/Single-Analysis Approach to Substrate Scope Investigations Using Comprehensive Two-Dimensional Gas Chromatography (GC×GC)

• Published in: Journal of organic chemistry 2016-05, Vol.81 (9), p.3533-3541
• Main Authors: O’Neil, Gregory W, Nelson, Robert K, Wright, Alicia M, Reddy, Christopher M
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b00050

A representative substrate scope investigation for an enantioselective catalytic ketone-reduction has been performed as a single reaction on a mixture containing equimolar amounts of nine (9) prototypical compounds. The resulting analyte pool containing 18 potential products from nine different reactions could all be completely resolved in a single chromatographic injection using comprehensive two-dimensional gas chromatography (GC×GC) with time-of-flight mass spectrometry, allowing for simultaneous determination of percent conversion and enantiomeric excess for each substrate. The results obtained for an enantioselective iron-catalyzed asymmetric transfer hydrogenation using this one-pot/single-analysis approach were similar to those reported for the individualized reactions, demonstrating the utility of this strategy for streamlining substrate scope investigations. Moreover, for this particular catalyst, activity and selectivity were not greatly affected by the presence of other ketones or enantioenriched reduced products. This approach allows for faster and greener analyses that are central to new reaction development, as well as an opportunity to gain further insights into other established transformations.