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

Abstract

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.

Recent Progress on One-Pot Multisubstrate Screening

“…They used this method to test the reduction of nine ketone substrates 14e , 14i , 14j , and 14m – r , investigated by the Li and Gao group, to their corresponding alcohols 15e , 15i , 15j , and 15m – r in a one-pot fashion (Scheme ). The ee values were quite similar, and the % conversions followed the same trend between substrates even though they were not always so close to the previously reported single-substrate trials . This is probably the first example of using GC × GC in OPMSS (Figure ).…”

“…The ee values were quite similar, and the % conversions followed the same trend between substrates even though they were not always so close to the previously reported single-substrate trials. 30 This is probably the first example of using GC × GC in OPMSS ( Figure 14 ). The GC × GC technology has excellent potential in OPMSS; however, it has not been used in organic synthesis, possibly because of the scarcity of equipment.…”

“… GC × GC chromatogram of 9 ketones and the resulting 18 reduction products. Modified with permission from ref ( 30 ). Copyright 2016 American Chemical Society.…”

Accessing Monomers, Surfactants, and the Queen Bee Substance by Acrylate Cross‐Metathesis of Long‐Chain Alkenones

“…GC × GC has a history of success in analyzing exceedingly complex mixtures of compounds, particularly for petroleum research [38], but more recently it has been applied to reaction development [39]. The technique uses two serially joined columns, whereby all compounds eluting from the first are trapped and then reinjected onto the second.…”