
Proving the Configuration of Glucose and Synthesizing Two Unnatural Products
Michael McBride's Freshman Organic Chemistry II lecture at Yale (CHEM 125B) traces how chemists determined glucose's structure before modern spectroscopy existed. McBride opens with IR, NMR, and X-ray views of glucose's pyranose ring, then walks back to 1887, when Heinrich Kiliani established glucose as an aldohexose and, with Emil Fischer, developed a method for homologating aldoses. He details Fischer's use of crystalline osazones and his Fischer projections to argue, in 1892, which of eight possible aldohexose configurations matches glucose, a proof that also validated van't Hoff's stereochemical theory. The lecture closes with a different synthesis problem: Cram, Tanner, and Thomas's 1991 preparation of antiaromatic cyclobutadiene inside a custom-built clamshell molecule, isolating a molecule too reactive to exist freely, and their NMR evidence for its antiaromaticity. Chapter markers separate the historical proof from the modern synthesis.