Regio- and Chemoselective One-Step 3-O-Alkylenation of Unprotected Ascorbic Acid Using ω-Iodoalkanols

A regio- and chemoselective alkylenation employing unprotected ascorbic acid and a series of unprotected iodoalkanols in the presence of sodium hydrogen carbonate in dimethyl sulfoxide is described. This atom economic high yielding procedure delivers the corresponding 3-O-alkylene ethers in a single step without prior protection. Specific 3-O-etherification was also observed with unprotected 16-iodohexadecanoic acid and with 2-(10-iododecyl)isoindole-1,3-diotic. Furthermore, an 2-O-alkylene derivative was obtained when 3-O-benzyl ascorbic acid was reacted with unprotected 10-iododecanol under slightly modified conditions. Finally, the antioxidative activity of all compounds was determined and compared to vitamin C and E.