Lessons in Stereochemistry: Resolution, Synthesis, and Characterization of Chiral Compounds

Abstract

This modular, open-framework capstone course delves deeply into the synthesis, separation, and characterization of chiral molecules while teaching critical thinking and writing skills in a research-like setting within a fertile area for discovery. This course has evolved over 30 years and has been in its present form for 5 years at the time of this writing. The studies described can be easily integrated into a curriculum with other related disciplines, including medicinal, synthetic, analytical, and physical chemistry. The first procedure introduces Pasteur’s classic resolution of (±)-α-phenylethylamine by cocrystallization with enantio-pure d-tartaric acid. The enantiomerically enriched α-phenylethylamine is then characterized using three different methods: polarimetry to measure [α]D, high-performance liquid chromatography (HPLC) with a chiral column to determine the enantiomeric ratio (e.r.), and by proton nuclear magnetic resonance (1H NMR) using a chiral shift reagent. In the second experiment, students carry out a stereoselective alkylation of a glycine Schiff base using a cinchonine-derived phase-transfer catalyst and methods first developed by O’Donnell and expanded on by many other chemists around the world. The students are encouraged to read the primary literature and design their own experiments with the guidance of the instructors and graduate student teaching assistants (TAs). In our course, the first experiment is described as a communication and the alkylation experiment is reported in the format of a full paper.