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. Only one stereoisomer of these compounds is active, while the other is inactive or toxic. Our goal is to determine reaction conditions and substrate characteristics that lead to one stereoisomer preferentially to the others. Here we focus on an oxazolidine starting material with an electron-withdrawing substituent (tosylate) at the nitrogen center and a bulky substituent (phenyl) at the alpha position. While the presence of the bulky substituent increases the activation barrier of most steps in the mechanism, it does not effectively select for one stereoisomer. In addition, the electron-withdrawing substituent at the iminium center increases the activation barrier for the initial, oxazolidine-opening step of the reaction. Consequently, the step where stereochemistry is determined is no longer rate determining.

Effect of bulky substituents with varying electronic characteristics on the stereoselective synthesis of substituted pyrrolidines

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.