The Pd/C-catalyzed efficient and regioselective hydrogen-deuterium (H-D) exchange reaction on the benzylic site proceeded in D2O in the presence of a small amount of H2 gas. The use of the Pd/C-ethylenediamine complex [Pd/C(en)] as a catalyst instead of Pd/C led to the efficient deuterium incorporation into the benzylic site of O-benzyl protective groups without hydrogenolysis. These H-D exchange reactions provide a post synthetic and D(2)-gas-free deuterium-labeling method on a wide variety of benzylic sites using D2O as the deuterium source and heterogeneous Pd/C or Pd/C(en) as a reusable heterogeneous palladium catalyst under mild and neutral conditions.

The Pd/C-catalyzed H(2)-D(2) exchange reaction using a H(2)-D(2)O combination provided a general, efficient and environmentally friendly route for the preparation of deuterium gas (D(2)). H(2) sealed in a reaction flask was converted into nearly pure D(2), which could be used for the Pd/C-catalyzed one-pot reductive deuteration of various reducible functionalities and the chemoselective one-pot deuterogenation of olefin and acetylene. Additionally, we established the capturing method of the generated D(2) in a balloon, which was successfully applied to the Pd/C-catalyzed reductive mono-N-alkylation of a primary amine using nitrile as the alkylating reagent.