Organofluorine Compounds and Fluorinating Agents; 29: [1] Stereo­selective Synthesis and Reactivity of 2-Chlorodifluoromethyl-Substituted Mono­saccharides

Abstract

Chlorodifluoromethyl groups were introduced into the 2-position of the glycals 1, 5, 8, and 11 by dithionite-mediated addition of CF₂ClBr. The reaction proceeded stereoselectively, i.e. the CF₂Cl-group is always found trans to the neighbouring substituent at C-3 in the products. Because the primarily formed glycosyl bromides hydrolyse easily, the corresponding 2-chlorodifluoromethyl-2-deoxypyranoses 3, 6, 9, and 12 were isolated. Only 3,4,6-tri-O-acetyl-2-chlorodifluoromethyl-2-deoxy-d-glucopyranosyl bromide (2) was stable enough for chromatographic separation. The unprotected anomeric pyranoses 3, 6, 9, and 12 were acetylated by acetic anhydride/pyridine yielding the 1-O-acetyl derivatives 4, 7, 10, and 13. These compounds are suitable glycosyl donors, just as the anomeric phenyl thioglycosides 16 and 17 generated from 1,3,4-tri-O-acetyl-2-chlorodifluoromethyl-2-deoxy-d-arabinopyranside (7) and thiophenol (BF₃-catalysis). Furthermore, the reactivity of glucosyl bromide 2, 6-deoxy-l-glucose derivative 13 and thioglycosides 16, 17 was investigated. On treatment of glucosyl bromide 2 with pyridine, the 2-chlorodifluoromethyl substituted glycal 14 is formed as the result of HBr elimination. Furthermore, the chlorodifluoromethyl group of compounds 14 and 16 was converted into a methoxycarbonyl group by refluxing in methanolic sodium methoxide (products 15 and 19, respectively). Finally, the thioglycosides 16 and 17 were subsequently deacetylated by CsF on alumina (yielding the dihydroxy derivatives 18 and 20) and acetalized with chloral/DCC (18 forming acetal 21 and carbonate 22) and acetone (20 forming acetal 23), respectively. X-ray analyses are given for the 1-O-acetate 4 and the thioglycosides 21 and 24.

Key words

carbohydrates - glycals - difluoromethylation - radical addition reactions - eliminations - acetals

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Part 28: Schwäbisch, D.; Miethchen, R. J. Fluorine Chem. 2002, in press.

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Part 28: Schwäbisch, D.; Miethchen, R. J. Fluorine Chem. 2002, in press.

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Treatment of thioglycoside 16 with Zemplén reagent at r.t. for 12 h gave a mixture of 18 and 19 (ratio, ca. 3:1).

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Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC 198524-198526. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax [phone] or e-mail: [e-mail]) or via www.ccdc.cam.ac.uk/conts/retrieving.html.