Modular Construction of Chiral Aminopiperidine via Palladium-Catalyzed Hydroamination of 1,2-Dihydropyridine

In this study, we describe a generally straightforward methodology for the catalytic synthesis of chiral aminopiperidine from pyridine and azoles. The key step was the palladium-catalyzed regioselective N-H insertion into the double bond of 1,2-dihydropyridine. This hydroamination exhibits a wide substrate scope and functional group compatibility. Mechanistic study revealed that the catalytic N-H insertion into the C═C bond followed <i>cis</i> addition. The utility of this protocol was demonstrated by diverse functionalization of the enamine double bond.