Radical Trifluoromethylation of a d-Mannose Derived Ketene Dithioacetal. Synthesis of 2-C-Trifluoromethyl Derivatives of d-glycero-d-galacto- and d-glycero-d-talo-Heptopyranose

Abstract

Diacetone D-mannose was converted into ketene dithioacetals 3 by a Peterson reaction with 2-lithio-2-(trimethylsilyl)-1,3-dithiane or lithiobis(methylsulfanyl)(trimethylsilyl)methane. Radical addition of trifluoromethyl bromide (iodide) induced by electron transfer (from sulfoxylate radical anion) led selectively to a dithioketalized 2-deoxy-2-C-(trifluoromethyl)-D-glycero-D-galacto-heptopyranolactone (5a) or to the corresponding dithioketalized open sugar 9, mainly according to the alkylsulfanyl group. Reaction conditions were found for complete or partial dethioketalization of these intermediates. A diisopropylidene-protected 2-deoxy-2-C-(trifluoromethyl)-D-glycero-D-taloheptopyranolactone (12) was obtained from 5a, with concomitant epimerization of C-2. Compound 9 was converted into either the corresponding sugar 14 or its methyl thioglycoside 13. Most of these reactions gave preparative yields, and the overall sequence constitutes a three-step synthesis of 2-deoxy-2-C-(trifluoromethyl)-D-glycero-D-galacto-heptose or D-talo-heptose derivatives.

Strategies for nucleophilic, electrophilic, and radical trifluoromethylations

“…The reaction is promoted by sodium dithionite and related reagent systems [126][127][128]. Application to this reaction in sugar chemistry was reported by Portella and co-workers [129,130]. More recently, we described the radical trifluoromethylation of ammonium enolates of a series of 1,3-dicarbonyl compounds with CF 3 I in the presence of sodium dithionite in CH 3 CN-H 2 O solution.…”

Xanthates derived from 1,3-dithiane and its monosulfoxide; one-carbon radical equivalents

“…Silica gel 60 Å C. (11). A solution of 1 (23.9 g, 100 mmol) in CH 2 Cl 2 (200 mL) was cooled to 0 8C under a nitrogen atmosphere, before dropwise addition of a solution of mCPBA (24.9 g, 106 mmol) in CH 2 Cl 2 (225 mL).…”

Radicals in Carbohydrate Chemistry

“…Radical conjugate addition to enolone 58 occurred with equatorial selectivity and radical migration of the 0-2 benzoyl to 0-3 [48]. Trifluoromethyl radical addition to the open-chain ketene thiacetal 59 provides a convenient route to 2-C-trifluoromethyl derivative 60 [49].…”