Facile and convenient method of deuterium gas generation using a Pd/C-catalyzed H2-D2 exchange reaction and its application to synthesis of deuterium-labeled compounds.

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.

Efficient and convenient heterogeneous palladium-catalyzed regioselective deuteration at the benzylic position.

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.

Efficient h/d exchange reactions of alkyl-substituted benzene derivatives by means of the Pd/C-H(2)-D(2)O system.

A method for efficient and extensive H/D exchange of substituted benzene derivatives which is catalyzed by heterogeneous Pd/C in D(2)O as a deuterium source under hydrogen atmosphere is described. Multi-deuterium incorporation into unactivated linear or branched alkyl chains that bear a carboxyl, hydroxyl, ether, ester, or amide moiety and are connected with a benzene ring was achieved by using the Pd/C-H(2)-D(2)O system. The present method does not require expensive deuterium gas or any special equipment.

Complete replacement of H2 by D2 via Pd/C-catalyzed H/D exchange reaction.

[reaction: see text] A general and in situ D2 gas generation method using 10% Pd/C-catalyzed H2-D2 exchange reaction in a H2-D2O system has been developed. H2 gas sealed in a reaction flask was efficiently converted into nearly pure D2 gas, which can be used for the reductive deuteration of substrates possessing reducible functionalities within the molecule.

Efficient C-H/C-D exchange reaction on the alkyl side chain of aromatic compounds using heterogeneous Pd/C in D2O.

[reaction: see text] An efficient and extensive deuterium incorporation using heterogeneous Pd/C-D(2)O-H(2) system into many different types of unactivated C-H bond positions was developed. The present method provides a deuterium gas-free, totally catalytic, and post-synthetic deuterium labeling method in D(2)O media.

Palladium-catalyzed H-D exchange into nucleic acids in deuterium oxide.

We have developed an efficient and extensive deuterium incorporation method using a heterogeneous Pd/C-D2O-H2 system into the base moiety of nucleic acids. The results presented here provide a deuterium gas-free, totally catalytic and post-synthetic deuterium labeling method in D2O media.