Adaptation of Chiral GC into existing undergraduate labs to improve student appreciation of stereochemistry

Abstract

The critical role of stereochemistry in life, medicine, and industry mandates that stereochemistry is well represented in undergraduate lab curricula. This has primarily been achieved via experiments in the enantiomeric resolution of asymmetric acids and bases followed by polarimetric analysis, NMR analysis using chiral shift reagents, and NMR, GC, and HPLC analysis of diastereomeric derivatives of the chiral molecules. Despite the increasing prevalence of the utility of GCs and LCs fitted with chiral columns in academia and the chemical industry, they have seen limited involvement in undergraduate training. To achieve the stereochemical laboratory requirements without sacrificing existing lab techniques, we have modified two standard laboratory experiments to include chiral GC analysis as follows: (1) The extraction of carvone from spearmint leaves and caraway seeds via steam distillation or other extraction methods is a lab widely used to demonstrate stereochemistry. However, the analysis of the products from the extraction is often limited to thin-layer chromatograms that confirm the presence of carvone and shows that the enantiomers have similar polarity. By including a GC method using a β-DEX™ 225 column in this lab, students were able to compare retention times of the spearmint and caraway extracts with those in a racemic mixture, then predict whether they are R or S by comparing with an injection of a pure R-carvone sample. (2) The reduction of aldehydes and ketones is another common experiment done in most institutions. Sodium borohydride reduction of acetophenone produced a racemic mixture which was observed as two retention times on the chromatogram. Reduction using the two enantiomers of commercially available CBS catalysts provided relatively enantiopure alcohols. Students could predict which enantiomers resulted from each enantiomer of the CBS catalyst by comparing it with a commercially obtained enantiopure alcohol. They also used chromatographic data to calculate the enantiomeric excess from their reactions. The experiments also teach students other essential techniques like inert-atmosphere techniques, thin-layer chromatography, the use of multivendor software for analysis, and the effect of reaction conditions on product yield and stereochemistry