O-Benzyl group is one of the most common hydroxyl protective groups and deprotected easily by the catalytic hydrogenation using Pd/C. Deuterium labeled compounds at the benzylic position of O-benzyl groups are widely applicable. In particular, simplification of a ¹H NMR chart is valuable in the field of sugar chemistry. However, benzyl bromide or chloride-a,a-d₂ as a synthon of deuterium-labeled O-benzyl ethers is quite expensive.

We recently have published regioselective H-D exchange reaction on a benzylic carbon using Pd/C-D₂O-H₂ system while it is not applicable to substrates bearing reducible functionalities such as O-benzyl groups and so on. By the way, we also reported the chemoselective hydrogenation method with retention of the O-benzyl protective group using Pd/C-ethylenediamine complex [Pd/C(en)] as a catalyst.

Hence, we began to develop benzylic site selective H-D exchange reaction of the O-benzyl protective group using Pd/C(en)-D₂O-H₂ system. The present method is easily applicable to synthesis of various O-benzyl protected compounds bearing deuterated benzylic site in excellent deuterium efficiencies and chemical yields.