Oxidative Deprotection of Benzyl Protecting Groups for Alcohols by an Electronically Tuned Nitroxyl-Radical Catalyst

The oxidative deprotection of benzyl (Bn) groups using nitroxyl-radical catalyst 1 and co-oxidant phenyl iodonium bis(trifluoroacetate) (PIFA) is reported. This catalyst is highly active for the oxidation of benzylic ethers because of the electronic tuning on account of the electron-withdrawing ester groups next to the catalytically active center. This catalytic system promotes deprotections at ambient temperature and has a broad substrate scope, including substrates possessing hydrogenation-sensitive functional groups, while the deprotection hardly proceeds when using well-known nitroxyl-radical catalysts such as 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO). The 1/PIFA system also promotes the deprotection of several benzylic protecting groups, including 2-naphthylmethyl (NAP) and 4-methylbenzyl (MBn) groups. Catalyst 1 was also effective for the direct synthesis of ketones and aldehydes from Bn ethers via deprotected alcohols using an excess of the co-oxidant PIFA.