Microscale Synthesis of a Diphenylisoxazoline by a 1,3-Dipolar Cycloaddition

This microscale synthesis of a diphenylisoxazoline gives students an opportunity to prepare and examine the heterocyclic product of a pericyclic 1,3-dipolar addition reaction analogous to a Diels-Alder reaction. Two reaction pathways are proposed, one leading to 3,4-diphenylisoxazoline and the other to 3,5-diphenylisoxazoline. The ¹H NMR spectrum of the actual product is used to determine its structure and thus the reaction pathway. The proposed products have diasteriotopic hydrogens that are readily observed in the ¹H NMR spectra. Molecular modeling also is used to predict which product is more probable and to offer a likely explanation for the regioselectivity of the reaction.