Palladium-Catalyzed Asymmetric Remote Hydroamination of Internal Alkenes

Abstract

Asymmetric catalytic hydroamination of alkenes represents one of the most efficient strategies for constructing chiral N-heterocycles. Herein, we realize the asymmetric intramolecular remote hydroamination of internal cis-alkenes via palladium catalysis. The reaction proceeds through sequential alkene aminopalladation, palladium migration, and reduction of terminal alkyl-palladium intermediates. The corresponding nitrogen-containing heterocycles are furnished in good yields with high enantioselectivity, offering a straightforward and robust route to the synthesis of piperidone, pyrrolidone, and oxazolidin-2-one scaffolds. Detailed mechanistic studies disclose that the stereochemical outcome and reversibility of aminopalladation are strongly solvent-dependent. Furthermore, the reduction of the alkyl–Pd(II) bond is highly susceptible to steric hindrance, which enables the achievement of remote asymmetric hydroamination.