Skeletal rearrangements resulting from reactions of 1,6:2,3- and 1,6:3,4-dianhydro-β-d-hexopyranoses with diethylaminosulphur trifluoride

Abstract

A complete series of eight 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses were subjected to fluorination with DAST. The 1,6:3,4-dianhydropyranoses yielded solely products of skeletal rearrangement resulting from migration of the tetrahydropyran oxygen (educts of D-altro and D-talo configuration) or of the 1,6-anhydro bridge oxygen (D-allo, D-galacto). The major products yielded by the 1,6:2,3-dianhydropyranoses were compounds arising from nucleophilic substitution, with configuration at C4 either retained (D-talo, D-gulo) or inverted (D-manno), or from C6 migration (D-allo). The minor products in the 1,6:2,3-series resulted from migration of the tetrahydropyran oxygen (D-gulo) or the oxirane oxygen (D-manno), or from nucleophilic substitution with retention of configuration (D-manno). The structure of most of the rearranged products was verified by X-ray crystallography.

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

“…To prevent azide reduction, oxidative debenzylation [ 24 ] was applied instead of the more common hydrogenation. Debenzylation of 10 gave dianhydro derivative 13 [ 34 , 37 ] (available also directly from D-glucal [ 31 , 33 ] or from levoglucosan [ 38 ]) which was converted to 14 by Latrell–Dax inversion at C-4 [ 39 ]. O -Benzylation [ 40 ] of 14 followed by azidolysis [ 41 ] furnished 15 .…”

“…Since fluorination of 12 with DAST failed to introduce fluorine at C-4β due to formation of orthoester 25 , the reaction of 1,6:2,3-dianhydro-β-D-talopyranose 14 with DAST was utilized to give 1,6:2,3-dianhydro-4-deoxy-4-fluoro-β-D-talopyranose ( 30 ) with retention of the configuration at C-4 [ 39 ]. Azidolysis of the oxirane ring in the reaction with lithium azide furnished 2-azido derivative 31 .…”

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

“…We initially supposed that DAST, a commonly used reagent to install fluorine atoms on the carbohydrate core, would be suitable for the C4 deoxyfluorination of intermediates 2-5. However, it is well documented that undesired rearrangement products with 1,2-aglycone migration [26][27][28] or skeletal rearrangements [29] have been observed during fluorodeoxygenation of glycopyranosides with DAST. Nevertheless, we investigated the preparation of 1,6-anhydro-2,3,4-trideoxy-2,3,4-trifluoro-β-ᴅhexopyranose analogues from previously described 1,6anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-hexopyranoses 2-5 using DAST ( Table 1).…”

“…To account for the retention of configuration (minor product) in the fluorination of compound 13, we proposed the involvement of an oxiranium-like intermediate A (Figure 3b). Interestingly, oxiranium ions in carbohydrate chemistry have been proposed as intermediates in the course of various reactions [20,29,35,36]. An equatorial fluorine atom at C2 (antiperiplanar to the C1-O5 bond) reduces the endocyclic oxygen polarizability, but also destabilizes a possible carbocation at C4 (the C2-F2 bond is antiperiplanar to the C3-C4 bond) [37].…”

Synthesis of vicinal dideoxy-difluorinated galactoses

“…To a solution of 1,6:2,3-dianhydro-4-deoxy-4-fluoro-β-Dgulopyranose 18 32 (447 mg, 3.1 mmol) in ethylene glycol (7 mL) in a sealed tube and under argon, was added KF (1.09 g, 18.8 mmol) and KHF2 (1.40 g, 17.9 mmol). The mixture was stirred at 175 °C.…”