Reactions of 2-Hydroxy-6,8-dioxabicyclo[3.2.1]oct-3-ene with Diethylaminosulfur Trifluoride and with Halogens. Facile Synthesis of 1,6-Anhydrohalohexopyranoses

Abstract

D-Galactal 1 reacts in THF in the presence of catalytic amounts of concentrated sulfuric acid to give (2R)-2-hydroxy-6,8dioxabicyclo[3.2.1]oct-3-ene (4) in a Ferrier-type rearrangement in 40% yield. When 4 is treated with diethylaminosulfur trifluoride (DAST) under certain reaction conditions, a novel intramolecular second order allylic rearrangement follows leading to previously unknown diastereomeric monofluoro derivatives 7 and 8. Direct asubstitution of 4 by DAST affords the 2-monofluoro derivative 6 under kinetic control. When DAST is used with dimethylformamide as solvent an apparent [1,3] sigmatropic migration of the 2-hydroxy group of 4 gives (4S)-4-hydroxy-6,8-dioxabicyclo[3.2.1]oct-2-ene (9). The corresponding 4-fluoro-substituted product was not obtained from the reaction of 9 with DAST. Oxidation of 4 and repeated treatment with DAST gives a novel 2,2-difluoro compound 11. Electrophilic addition of bromine to protected 4 afforded the 1,6anhydromonobromo-and-dibromohexopyranoses 15-17. Monohalo and monopseudohalo derivatives (-F,-Cl,-Br,-N 3) 22-25 were prepared by nucleophilic oxirane ring opening of the easily available endo-epoxides 18-20.

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

“…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 . 2-Azido-3,4-epoxide 18 was prepared from readily available [ 42 ] 2,3-isopropylidene-D-mannosan ( 16 ) in five steps ( Scheme 2 ).…”

A Convenient Route to Peracetylated 3-Deoxy-3-fluoro Analogues of d-Glucosamine and d-Galactosamine from a Černý Epoxide

“…Azidolysis gave known 15 (Scheme 4). 15 However, treatment of 15 with DAST (in boiling benzene or in dichloromethane at r.t.), failed to produce the desired 3-fluoro derivative 16 (Scheme 4). The starting 15 was recovered whereas prolonged reaction resulted in a very slow formation of a mixture of several unknown fluorinated products as indicated by 19 This difficulty was overcome by placing the inversion of configuration after fluorination in the reaction sequence (Scheme 5).…”