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

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-talo-heptopyranolactone (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.