General Light-Mediated, Highly Diastereoselective Piperidine Epimerization: From Most Accessible to Most Stable Stereoisomer
Zican Shen, Morgan M. Walker, Shuming Chen, Giovanny A. Parada, Duc Chu, Sun Dongbang, James M. Mayer, K. N. Houk, Jonathan A. Ellman
Abstract
We report a combined photocatalytic and hydrogen atom transfer (HAT) approach for the light-mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di- to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.