Ring opening of sugar-derived epoxides by TBAF/KHF 2 : An attractive alternative for the introduction of fluorine into the carbohydrate scaffold

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

“…neat at 180 °C for 24 h led to the formation of 1,6-anhydro-2,4-dideoxy-2,4-difluoroglucopyranose 49 in 60% yield. 65 This procedure successfully allowed the stereoselective incorporation of two fluorine atoms placed 1,3- syn on a pyranose ring. The formation of intermediates 50 − 52 may be speculated to rationalize this transformation.…”

Synthesis of 4‐Deoxy‐4‐Fluoro‐d‐Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping

“…[27,28] The obtained mannoepoxide 2 was then opened in a trans-diaxial fashion with N,N,N,N-tetrabutylammonium fluoride trihydrate (TBAF×3 H 2 O) and potassium bifluoride on a gram-scale to give compound 3 as a single regioisomer. [25] Selective reductive opening of the benzylidene acetal at position 6 was achieved by the protocol described by Shie et al [29] and subsequent benzylation of the resulting diol gave fully protected altro-pyranoside 5. The methyl glycoside was then hydrolyzed under acidic conditions [30] to give the corresponding lactol which could be smoothly oxidized to lactone 7 with Dess-Martin periodinane (DMP).…”

“…The black suspension was degassed (3 freezing/thawing cycles with liquid N 2 under vacuum) and subsequently stirred at room temperature for 24 h (completion of the reaction was verified by absence of aromatic proton signals in d 4 -methanol after drying a small portion of the reaction mixture in high vacuum). The mixture was filtered, evaporated, and purified by reversed-phase chromatography (C 18 -modified silica gel, H 2 O) yielding 4-deoxy-4-fluoro-dsedoheptulose (4DFS) as a colorless oil and as a mixture of α-and β-furanoses and α-and β-pyranoses in a 1.5 :4 : 4 : 1 ratio (60 mg, 80 %); R f = 0.7 (1-BuOH/acetone/H 2 O 5 : 4 : 1, CAM); ½a� 20 D = + 23.4 (c = 1.0 in H 2 O); β-Furanose: 1 H NMR (700 MHz, D 2 O) δ = 5.17 (dt, 2 J 4,F = 56.4 Hz, 3 J 4,3 = 6.1 Hz, 3 J 4,5 = 5.1 Hz, 1H, H-4), 4.42 (dd, 3 J 3,F = 22.7 Hz, 3 J 3,4 = 6.1 Hz, 1H, H-3), 4.00 (ddd, 3 J 5,F = 21.4 Hz, 3 J 5,6 = 7.8 Hz, 3 J 5,4 = 5.1 Hz, 1H, H-5), 3.82 (ddd, 3 J 6,5 = 7.8 Hz, 3 J 6,7b = 6.2 Hz, 3 J 6,7a = 3.3 Hz, 1H, H-6), 3.76 (dd, 2 J 7a,7b = 11.9 Hz, 3 J 7a,6 = 3.3 Hz, 1H, H-7a), 3.62 (dd, 2 J 7b,7a = 11.9 Hz, 3 J 7b,6 = 6.2 Hz, 1H, H-7b), 3.59 (dd, 2 J 1a,1b = 12.1 Hz, 5 J 1a,F = 0.7 Hz, 1H, H-1a), 3.55 (dd, 2 J 1b,1a = 12.1 Hz, 5 J 1b,F = 1.7 Hz, 1H, H-1b); 13 J 4,3 = 3 J 4,5 = 3.2 Hz, 1H, H-4), 4.10 (ddd, 3 J 6,5 = 10.5 Hz, 3 J 6,7b = 5.8 Hz, 3 J 6,7a = 2.4 Hz, 1H, H-6), 4.06 (dd, 3 J 3,F = 6.0 Hz, 3 J 3,4 = 3.2 Hz, 1H, H-3), 3.88 (ddd, 3 J 5,F = 31.1 Hz, 3 J 5,6 = 10.5 Hz, 3 J 5,4 = 3.2 Hz, 1H, H-5), 3.87 (dd, 2 J 7a,7b = 12.2 Hz, 3 J 7a,6 = 2.4 Hz, 1H, H-7a), 3.75 (dd, 2 J 7b,7a = 12.2 Hz, 3 J 7b,6 = 5.8 Hz, 1H, H-7b), 3.70 (d, 2 J 1a,1b = 11.7 Hz, 1H, H-1a), 3.53 (d, 2 J 1b,1a = 11.7 Hz, 1H, H-1b); 13 J 4,F = 52.9 Hz, 3 J 4,5 = 3.8 Hz, 3 J 4,3 = 2.2 Hz, 1H, H-4), 4.33 (dd, 3 J 3,F = 16.2 Hz, 3 J 3,4 = 2.2 Hz, 1H, H-3), 4.24 (ddd, 3 J 5,F = 24.0 Hz, 3 J 5,6 = 6.7 Hz, 3 J 5,4 = 3.8 Hz, 1H, H-5), 3.80 (td, 3 J 6,5 = 3 J 6,7b = 6.7 Hz, 3 J 6,7a = 3.6 Hz, 1H, H-6), 3.74 (ddd, 2 J 7a,7b = 12.0 Hz, 3 J 7a,6 = 3.6 Hz, 5 J 7a,F = 0.4 Hz, 1H, H-7a), 3.72 (d, 2 J 1a,1b = 12.0 Hz, 1H, H-1a), 3.66 (d, 2 J 1b,1a = 12.0 Hz, 1H, H-1b), 3.62 (dd, 2 J 7b,7a = 12.0 Hz, 3 J 7b,6 = 6.7 Hz, 1H, H-7b); 13 3 J 3,F = 10.9 Hz, 3 J 3,4 = 8.3 Hz, 1H, H-3), 3.99 (dddd, 3 J 6,7a = 6.3 Hz, 3 J 6,7b = 6.0 Hz, 4 J 6,F = 4.3 Hz, 3 J 6,5 = 3.5 Hz, 1H, H-6), 3.80 (dd, 2 J 7a,7b = 12.0 Hz, 3 J 7a,6 = 6.3 Hz, 1H, H-7a), 3.77 (dd, 2 J 7b,7a = 12.0 Hz, 3 J 7b,6 = 6.0 Hz, 1H, H-7b), 3.71 (dd, 2 J 1a,1b = 11.9 Hz, 5 J 1a,F = 1.0 Hz, 1H, H-1a), 3.57 (dd, 2 J 1b,1a = 11.9 Hz, 5 J 1b,F = 1.9 Hz, 1H, H-1b); 13 were synthesized following a protocol by Shie et al [29] Methyl 4,6-Obenzyliden-2-deoxy-2-fluoro-α-d-altro-pyranoside [25,35] (12, 151 mg, 0.53 mmol, 1 equiv.) was dissolved in a borane THF complex solution (1 M in THF, 2.66 mL, 0.04 mmol, 5 equiv.)…”

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…Finally, the Dyatkina group at Janssen Biopharma synthesized the branched nucleoside 673 with 2’3′- ribo -difluorination (Scheme ). Starting from α- 633 , synthesized as shown in Scheme , conversion to the 2′,3′-anhydro derivative α- 635 was achieved via tosylation, acetonide removal, and cyclization, which was then protected as the benzyl ether α- 636 . ,, Opening of the epoxide with fluoride now proceeded with complete regioselectivity to give α- 638 , which will be due to the combined steric and electronic effects of the α-configured anomeric center . Tosylation of the OH-2 group allowed inversion of configuration with sodium benzoate in moderate yield .…”