Optimized Conditions for the Palladium-Catalyzed Hydrogenolysis of Benzyl and Naphthylmethyl Ethers: Preventing Saturation of Aromatic Protecting Groups

While carrying out palladium-catalyzed hydrogenolysis to deprotect synthetic oligosaccharides, saturation of the benzyl and naphthylmethyl ether groups to their corresponding ether was observed. In order to suppress this unwanted hydrogenation, we report a scalable practical approach using a catalyst pre-treatment strategy, which is effective under batch or continuous flow conditions. This suppressed the unwanted hydrogenation side-products and created a selective catalyst for hydrogenolysis of benzyl and naphthylmethyl ethers. We demonstrate the efficient deprotection of a set of structurally diverse oligosaccharides (5 examples, > 73 %).