Seven-membered ring boronates at trans-diol moieties of carbohydrates Marcel Meiland, Thomas Heinze, Wolfgang Guenther, Tim Liebert * Center of Excellence for Polysaccharide Research, Friedrich Schiller University of Jena, Humboldtstrasse 10, 07743 Jena, Germany article info Article history: Received 17 September 2008 Revised 6 November 2008 Accepted 12 November 2008 Available online 18 November 2008 Keywords: Phenylboronate 13 C NMR spectroscopy 11 B NMR spectroscopy trans-1,2-Diol Methyl-a-D-glucopyranoside abstract MS and 1 H, 13 C and 11 B NMR results are presented revealing the formation of cyclic seven-membered boronate structures at trans-1,2-diol moieties of carbohydrates providing new opportunities for the activation, protection and analysis of glucopyranose-based oligomers and polymers such as cellulose or starch. ‘Coordination-induced shifts’ in 13 C NMR spectra were identified for the esterification by boronic acids of carbohydrates, which can be applied for further studies. Ó 2008 Elsevier Ltd. All rights reserved. The interaction of widespread glucopyranose-based compounds with boric acid or its derivatives, for example, salts or boronic acids, is, in principle, very useful for the analysis, activation, pro- tection and cross-linking of carbohydrates; 1 however, in most cases the structures formed are poorly understood. In general, strong bonds with diol moieties of carbohydrates are formed, resulting in cyclic esters or complexes. 1,2 In the most abundant glu- copyranose-based oligomers and polymers, mainly the trans-1,2- diol system in positions 2 and 3 is available for a ring formation. Five- and six-membered rings are not reasonable because of high ring tension. Nevertheless, beneficial effects of boric acid or its salts as activating agents in commercial modification procedures of polyglucans such as cellulose are known but scarcely applied because of unpredictable reactions. 3–7 Controlled processes may result in new opportunities for the chemical modification and anal- ysis of glucopyranose-based compounds. In case of oligo- and poly- glucans, the so-called derivatizing solvents 8 could be accessible where dissolution occurs via intermediate formation of covalent bonds or complexes leading to soluble, instable derivatives suit- able for subsequent functionalization under defined homogeneous conditions. 9–11 Therefore, a basic understanding of the borate and boronate formation of glucopyranose-based compounds is indispensable. Although own NMR studies on mixtures of soluble cellodextrins converted with boric acid in DMSO yielded badly resolved spectra, the data indicated derivatization of the carbohydrates at the trans- diol moiety and fast transesterification reactions. In order to limit the structural diversity, the reaction of the relevant trans-diol moi- ety with a model system consisting of methyl-a-D-glucopyranoside (Me-a-D-glcp) and phenylboronic acid (PBA) was studied in detail. Different papers showed that Me-a/b-glcp binds the borate through their flexible hydroxyls in positions 4 and 6. 12,13 Conse- quently, only the diol structure at positions 2 and 3 of the mono- saccharide is accessible for further modification, making this system a reasonable model for the conversion of a oligo- or poly- glucan. For non-aqueous media, Ferrier first mentioned esterifica- tion of the secondary hydroxyls of Me-a-D-glcp with PBA after azeotropic distillation in the presence of benzene, but the products were only characterized by elemental analysis. 14,15 A seven-mem- bered ring including two boron atoms with the trans-1,2-diol moi- ety in positions 2 and 3 is suggested. Up to now, NMR spectroscopy was not able to confirm such a large ring system. 16 In a set of experiments, the transformation of Me-a-D-glcp with PBA was studied by means of mass spectrometry (MS). The phenyl- boronates (Fig. 1) were prepared by dissolving different ratios of dry carbohydrates and triphenylboroxole in a mixture of N,N- dimethylformamide and 2,2-dimethoxypropane, which may result in different molecular ions and fission products (Fig. 1). A solution of derivatized methyl-glycopyranoside was evaporated in the MS probe crucible, and was introduced into the mass spectrometer. The spectra were measured using electron impact (EI) ionization. 17 An equimolar conversion of Me-a-D-glcp with PBA yields a methyl-4,6-O-phenylboronate-a-D-glucopyranoside (1) that was confirmed by a peak for the molecular ion at m/z 280 and one fragment ion I at m/z 160 for a 1,3,2-dioxaborinane structure. If an excess of PBA is applied, the methyl-2,3-O-(diphenylpyroboro- nate)-4,6-O-phenylboronate-a-D-glucopyranoside (2) should be formed. The MS spectrum of the compound obtained shows signif- icant fragment ions at m/z 160 (I) and at m/z 250 (II) in addition to 0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2008.11.043 * Corresponding author. Tel.: +49 (0) 3641 948270; fax: +49 (0) 3641 948272. E-mail address: tim.liebert@uni-jena.de (T. Liebert). Tetrahedron Letters 50 (2009) 469–472 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet