Iridium-catalyzed Asymmetric Hydrogenation of Pyridinium Salts for Constructing Multiple Stereogenic Centers on Piperidines

摘要

A salt formation strategy for asymmetric hydrogenation of pyridines is described. Poly-substituted pyridinium salts were successfully hydrogenated using chiral iridium dinuclear complexes to afford substituted piperidines with multiple stereogenic centers after a simple basic workup. Chiral piperidine is an important structural skeleton abundant in a vast array of natural products and biologically active organic compounds, and it is often embedded within scaffolds of privileged structures recognized by medicinal chemists. In this context, tremendous efforts have been focused on the development of synthetic protocols for such a prevalent motif. Among them, asymmetric hydrogenation of substituted pyridines is the most straightforward and atom-economical route to concurrently constructing multiple stereocenters, but it remains a difficult task despite the recent report of the asymmetric hydrogenation of N-heteroaromatics.