A common sugar as model for many-sided natural product modification.: From D-fructose via D-tagatose to 2-C-chlorodifluoro-methylated D-arabinopyranos-5-ulose derivatives

Starting with 3,4-O-[(R)-2,2,2-trichloroethylidene]-1,2-O-isopropylidene-beta-D-tagatopyranose 2 obtained from 1,2-O-isopropylidene-beta-D-fructopyranose 1 by a non-classical one-step acetalization with chloral/DCC, the fluoroalkylated glycosyl donors 15 and 17 were synthesised in 3-4 steps. By this sequence, one stereogenic center was inverted, one new chiral center was introduced, and one stereogenic center, for the time being eliminated, was later re-introduced. The glycals 11 and 12, key intermediates of the synthesis sequence, were accessible from triflate precursors (e.g., 10) by treatment with DBU. Corresponding halogeno-(6, 7), tosyl-(5, 8), or mesyl-(9) precursors were unsuitable. The stereoselective introduction of a chlorodifluoromethyl group was realised by dithionite-mediated CF2ClBr-addition to the glycal double bond. Subsequently, either the chlorodifluoromethylated glycosyl bromide (13) or the corresponding pyranoses (14 and 16) were isolated. The latter were still acetylated to the 1-O-acetyl derivatives 15 and 17, respectively. An x-ray analysis is given for the 5-O-tosylate 8.