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Synlett 2009(2): 217-220  
DOI: 10.1055/s-0028-1087662
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Thierry Mullera, Paul Heuschlingb, Bang Luu*c
a Institut für Organische Chemie, Universität Karlsruhe (TH), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
b Laboratoire de NeuroBiologie, Unité de Recherche Sciences de la Vie, Faculté des Sciences, de la Technologie et de la Communication, Université du Luxembourg, 1511 Luxembourg, Luxembourg
c Laboratoire de Chimie Organique des Substances Naturelles, UMR 7177 CNRS, Université Louis Pasteur, 67084 Strasbourg Cedex, France
Fax: +33(388)411672; e-Mail: bang.luu@orange.fr;
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Publication History

Received 22 September 2008
Publication Date:
15 January 2009 (online)

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Abstract

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-dione. 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.

Key words

ascorbic acid - regioselective - chemoselective - 3-O-alkylenation - ω-iodoalkanols

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16

Typical Experimental Procedure; Preparation of ( R )-5-[( S )-1,2-Dihydroxyethyl)]-3-hydroxy-4-(10-hydroxy-decyloxy)furan-2 (5 H )-one (11b): Ascorbic acid (3.20 g, 18.20 mmol, 2.5 equiv) and NaHCO3 (1.83 g, 21.85 mmol, 3 equiv) were added to a solution of 10-iododecanol (2.07 g, 7.28 mmol, 1 equiv) in anhyd DMSO (18 mL) and the resulting mixture was heated at 60 ˚C. After 3 h, DMSO was evaporated under reduced pressure and the residue was suspended in ethanol (12 mL) and brine (12 mL). EtOAc (200 mL) was added to the suspension which was then dried over MgSO4, filtered and evaporated under reduced pressure. The crude was purified via silica gel column chromatography (CH2Cl2-MeOH, 9:1) and was recrystallized (EtOAc-hexane) to give a white solid (80%). R f = 0.30 (EtOAc); mp 71-73 ˚C. IR (CHCl3): 3396 (OH), 1748 (CyO), 1693 (CyO) cm-¹. ¹H NMR (300 MHz, CD3OD): δ = 1.31 (br s, 12 H, H-3′ to H-8′), 1.51 (m, 2 H, H-9′), 1.72 (m, 2 H, H-2′), 3.52 (t, J = 6.6 Hz, 2 H, H-10′), 3.64 (m, 2 H, CH2OH), 3.82 (m, 1 H, CHOH), 4.48 (m, 2 H, H-1′), 4.75 (d, J = 1.8 Hz, 1 H, CH). ¹³C NMR (75 MHz, CD3OD): δ = 25.2, 25.5 (C-2′, C-3′), 28.2-29.2 (C-4′ to C-8′), 32.2 (C-9′), 61.6 (CH2OH), 70.0 (CHOH), 70.5 (C-10′), 72.4 (C-1′), 75.2 (CH), 119.0 (=COH), 150.8 (=CO-alkyl), 171.8 (C=O).