Enantioselective Synthesis of Functionalized 2,2-Disubstituted Piperidines Enabled by Pd-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Herein, we report a palladium-catalyzed decarboxylative asymmetric allylic alkylation (Pd-DAAA) for the synthesis of enantioenriched 2,2-disubstituted piperidines. This method efficiently constructs aza-quaternary stereocenters with high enantioselectivity and broad functional group compatibility. Its utility is demonstrated through access to synthetically useful azacyclic building blocks, a formal synthesis of arbornamine, and the identification of potent antileukemia agents, establishing Pd-DAAA as a robust strategy for chiral piperidine and α-tertiary amine synthesis.