A New Hydroxyl Protecting Group

To manage a multitude of hydroxyl groups in sugars, carbohydrate chemists play a shell game of sorts, shuffling protecting groups to expose each alcohol at the right step in a synthesis. Researchers at the Hungarian Academy of Sciences have introduced a new protecting group to the mix (Org. Lett., DOI: 10.1021/ol100562f). Katalin Daragics and Péter Fügedi report that (2-nitro­phen­yl)acetyl (NPAc) works well at masking hydroxyl moieties. The NPAc groups are prepared from (2-nitrophenyl)acetic acid, an inexpensive commercially available compound, or the corresponding acid chloride or anhydride. The NPAc ester stands up to a series of common carbohydrate transformations and can be selectively removed in the presence of other popular hydroxyl protecting groups, such as tert-butyldimethylsilyl, levulinoyl, 9-fluorenylmethoxycarbonyl, naphthylmethyl, and p-methoxybenzyl. The deprotection step (shown) is what’s known as an assisted cleavage: Reduction of the auxiliary nitro group with zinc and ammonium chloride produces an ester of (2-amino­phen­yl)acetic acid, which intramolecularly attacks the ester bond to form an indolinone, releasing the alcohol in the process.