Ligand-free reductive amination via Pd-coated mechanocatalysis

Reductive amination under direct mechanocatalysis was enabled by a sequential two-frequency milling protocol, separating imine formation and hydrogenation. Strongly hydrophobic liquid additives accelerated the reaction by enhancing water exclusion. This approach allowed amine yields of up to 88% and was applicable to various aldehydes, ketones, and primary or secondary amines.