McNair Scholars Research Journal


In this work we use computational methods to study the aza-Cope-Mannich tandem reaction of a substituted oxazolidine to form a formyl pyrrolidine. Pyrrolidine structural motifs are found in natural products, pharmaceutical compounds, and chiral catalysts. Often only one stereoisomer of these compounds is active, while the others are inactive or toxic. Our goal is to determine reaction conditions and substrate characteristics that lead to one stereoisomer preferentially over the others. We focus on an oxazolidine starting material with an electron-withdrawing group at the nitrogen center and a bulky substituent at the alpha position. The long-term objective is to delineate the energy profile for the multi-step reaction of this starting material, to form a specific enantiomer of the pyrrolidine product. This will allow us to determine the effect of the electron-withdrawing group and the bulky substituent on the stereoselectivity of the reaction. The results will aid the experimental group of our collaborators in determining appropriate reaction conditions. Results to date indicate that the presence of the electron-withdrawing group at the nitrogen center increases the activation energy of the first step of the reaction. If this is in fact the rate-determining step, poor product stereoselectivity is expected, as stereochemistry is not established in this step.